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image of Synergistic Targeting of EGFR, ESR1, BCL2, and TP53 Pathways: A 
Multi-Pronged Approach for Advanced Breast Cancer Therapy

Abstract

Breast cancer is a heterogeneous disease driven by complex molecular signaling pathways that influence tumor progression, metastasis, and treatment resistance. This review provides a comprehensive analysis of the molecular mechanisms underlying breast cancer, with a focus on key pathways such as EGFR, ESR1, BCL2, and TP53. We examine the roles of these pathways in regulating critical cellular processes, including proliferation, survival, apoptosis, and migration. EGFR’s involvement in cell proliferation and migration, as well as its overexpression and mutations in breast cancer, are discussed, alongside the impact of ESR1 signaling in hormone-receptor-positive breast cancer and resistance to endocrine therapies. Additionally, the review highlights the function of BCL2 in apoptosis regulation and its overexpression in conferring resistance while also exploring the role of TP53 in cell cycle control and apoptosis, particularly its mutations that contribute to poor prognosis. Furthermore, the interplay between these molecular pathways-such as the crosstalk between EGFR and ESR1, BCL2-TP53 interactions, and the EGFR-TP53 mutational relationships-illustrates the complexity of resistance mechanisms and the need for multi-targeted therapeutic strategies. The concept of synergistic targeting, including the integration of the PI3K/AKT/mTOR pathway, is explored, with evidence supporting the potential for overcoming resistance and improving therapeutic outcomes. We also discuss the emerging role of personalized medicine, emphasizing biomarker-driven approaches for patient selection and tailored treatments. Finally, advancements in nanoparticle-based drug delivery systems are reviewed, addressing their potential to enhance therapeutic efficacy and address current challenges in cancer therapy. This review highlights the critical importance of understanding the molecular underpinnings of breast cancer and the need for integrated, multi-targeted approaches to overcome therapeutic resistance, offering insights into future directions for improving clinical outcomes in breast cancer treatment.

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2025-04-24
2025-09-05

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References

  1. Kimbung S. Johansson I. Danielsson A. Veerla S. Egyhazi Brage S. Frostvik Stolt M. Skoog L. Carlsson L. Einbeigi Z. Lidbrink E. Linderholm B. Loman N. Malmström P.O. Söderberg M. Walz T.M. Fernö M. Hatschek T. Hedenfalk I. Transcriptional profiling of breast cancer metastases identifies liver metastasis–selective genes associated with adverse outcome in Luminal a primary breast cancer. Clin. Cancer Res. 2016 22 1 146 157 10.1158/1078‑0432.CCR‑15‑0487 26276891
    [Google Scholar]
  2. Lakshmi Singh S. Vijayakumar M.R. Dewangan H.K. Lipid-based aqueous core nanocapsules (ACNs) for encapsulating hydrophilic vinorelbine bitartrate: Preparation, optimization, characterization, and in vitro safety assessment for intravenous administration. Curr. Drug Deliv. 2018 15 9 1284 1293 10.2174/1567201815666180716112457 30009708
    [Google Scholar]
  3. Yi M. Li T. Niu M. Luo S. Chu Q. Wu K. Epidemiological trends of women’s cancers from 1990 to 2019 at the global, regional, and national levels: A population-based study. Biomark. Res. 2021 9 1 55 10.1186/s40364‑021‑00310‑y 34233747
    [Google Scholar]
  4. Visvader J.E. Cells of origin in cancer. Nature 2011 469 7330 314 322 10.1038/nature09781 21248838
    [Google Scholar]
  5. Dagogo-Jack I. Shaw A.T. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 2018 15 2 81 94 10.1038/nrclinonc.2017.166 29115304
    [Google Scholar]
  6. Saleem M.Z. Alshwmi M. Zhang H. Din S.R.U. Nisar M.A. Khan M. Alam S. Alam G. Jin L. Ma T. Inhibition of JNK-mediated autophagy promotes Proscillaridin A- induced apoptosis via ROS generation, intracellular Ca+2 oscillation and inhibiting STAT3 signaling in breast cancer cells. Front. Pharmacol. 2020 11 01055 10.3389/fphar.2020.01055 33013353
    [Google Scholar]
  7. Yadav D. Dewangan H.K. Pegylation: An important approach for novel drug delivery systems. J. Biomater. Sci. Polym. Ed. 2020 3 1 15 32942961
    [Google Scholar]
  8. Chen W. Zheng R. Baade P.D. Zhang S. Zeng H. Bray F. Jemal A. Yu X.Q. He J. Cancer statistics in China, 2015. CA Cancer J. Clin. 2016 66 2 115 132 10.3322/caac.21338 26808342
    [Google Scholar]
  9. Kashyap A. Rapsomaniki M.A. Barros V. Fomitcheva-Khartchenko A. Martinelli A.L. Rodriguez A.F. Gabrani M. Rosen-Zvi M. Kaigala G. Quantification of tumor heterogeneity: From data acquisition to metric generation. Trends Biotechnol. 2022 40 6 647 676 10.1016/j.tibtech.2021.11.006 34972597
    [Google Scholar]
  10. Wu C.Y. Lau B.T. Kim H.S. Sathe A. Grimes S.M. Ji H.P. Zhang N.R. Integrative single-cell analysis of allele-specific copy number alterations and chromatin accessibility in cancer. Nat. Biotechnol. 2021 39 10 1259 1269 10.1038/s41587‑021‑00911‑w 34017141
    [Google Scholar]
  11. Gao W. Ku W.L. Pan L. Perrie J. Zhao T. Hu G. Wu Y. Zhu J. Ni B. Zhao K. Multiplex indexing approach for the detection of DNase I hypersensitive sites in single cells. Nucleic Acids Res. 2021 49 10 e56 10.1093/nar/gkab102 33693880
    [Google Scholar]
  12. Pott S. Simultaneous measurement of chromatin accessibility, DNA methylation, and nucleosome phasing in single cells. eLife 2017 6 e23203 10.7554/eLife.23203 28653622
    [Google Scholar]
  13. Network C.G.A. Comprehensive molecular portraits of human breast tumours. Nature 2012 490 7418 61 70 10.1038/nature11412 23000897
    [Google Scholar]
  14. Curtis C. Shah S.P. Chin S.F. Turashvili G. Rueda O.M. Dunning M.J. Speed D. Lynch A.G. Samarajiwa S. Yuan Y. Gräf S. Ha G. Haffari G. Bashashati A. Russell R. McKinney S. Langerød A. Green A. Provenzano E. Wishart G. Pinder S. Watson P. Markowetz F. Murphy L. Ellis I. Purushotham A. Børresen-Dale A.L. Brenton J.D. Tavaré S. Caldas C. Aparicio S. METABRIC Group The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups. Nature 2012 486 7403 346 352 10.1038/nature10983 22522925
    [Google Scholar]
  15. Eirew P. Steif A. Khattra J. Ha G. Yap D. Farahani H. Gelmon K. Chia S. Mar C. Wan A. Laks E. Biele J. Shumansky K. Rosner J. McPherson A. Nielsen C. Roth A.J.L. Lefebvre C. Bashashati A. de Souza C. Siu C. Aniba R. Brimhall J. Oloumi A. Osako T. Bruna A. Sandoval J.L. Algara T. Greenwood W. Leung K. Cheng H. Xue H. Wang Y. Lin D. Mungall A.J. Moore R. Zhao Y. Lorette J. Nguyen L. Huntsman D. Eaves C.J. Hansen C. Marra M.A. Caldas C. Shah S.P. Aparicio S. Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution. Nature 2015 518 7539 422 426 10.1038/nature13952 25470049
    [Google Scholar]
  16. Kim C. Gao R. Sei E. Brandt R. Hartman J. Hatschek T. Crosetto N. Foukakis T. Navin N.E. Chemoresistance evolution in triple-negative breast cancer delineated by single-cell sequencing. Cell 2018 173 4 879 893.e13 10.1016/j.cell.2018.03.041 29681456
    [Google Scholar]
  17. Sharma A.N. Upadhyay P.K. Dewangan H.K. Development, evaluation, pharmacokinetic and biodistribution estimation of resveratrol-loaded solid lipid nanoparticles for prostate cancer targeting. J. Microencapsul. 2022 39 6 563 574 10.1080/02652048.2022.2135785 36222429
    [Google Scholar]
  18. Lakshmi S.K. Singh S. Shah K. Dewangan H.K. Dual Vinorelbine bitartrate and Resveratrol loaded polymeric aqueous core nanocapsules for synergistic efficacy in breast cancer. J. Microencapsul. 2022 39 4 299 313 10.1080/02652048.2022.2070679 35470755
    [Google Scholar]
  19. Wu S.Z. Al-Eryani G. Roden D.L. Junankar S. Harvey K. Andersson A. Thennavan A. Wang C. Torpy J.R. Bartonicek N. Wang T. Larsson L. Kaczorowski D. Weisenfeld N.I. Uytingco C.R. Chew J.G. Bent Z.W. Chan C.L. Gnanasambandapillai V. Dutertre C.A. Gluch L. Hui M.N. Beith J. Parker A. Robbins E. Segara D. Cooper C. Mak C. Chan B. Warrier S. Ginhoux F. Millar E. Powell J.E. Williams S.R. Liu X.S. O’Toole S. Lim E. Lundeberg J. Perou C.M. Swarbrick A. A single-cell and spatially resolved atlas of human breast cancers. Nat. Genet. 2021 53 9 1334 1347 10.1038/s41588‑021‑00911‑1 34493872
    [Google Scholar]
  20. Chiu A.M. Mitra M. Boymoushakian L. Coller H.A. Integrative analysis of the inter-tumoral heterogeneity of triple-negative breast cancer. Sci. Rep. 2018 8 1 11807 10.1038/s41598‑018‑29992‑5 30087365
    [Google Scholar]
  21. Fisher R. Pusztai L. Swanton C. Cancer heterogeneity: Implications for targeted therapeutics. Br. J. Cancer 2013 108 3 479 485 10.1038/bjc.2012.581 23299535
    [Google Scholar]
  22. Sun X. Yu Q. Intra-tumor heterogeneity of cancer cells and its implications for cancer treatment. Acta Pharmacol. Sin. 2015 36 10 1219 1227 10.1038/aps.2015.92 26388155
    [Google Scholar]
  23. Jitariu A.A. Cîmpean A.M. Ribatti D. Raica M. Triple negative breast cancer: The kiss of death. Oncotarget 2017 8 28 46652 46662 10.18632/oncotarget.16938 28445140
    [Google Scholar]
  24. Bianchini G. Balko J.M. Mayer I.A. Sanders M.E. Gianni L. Triple-negative breast cancer: Challenges and opportunities of a heterogeneous disease. Nat. Rev. Clin. Oncol. 2016 13 11 674 690 10.1038/nrclinonc.2016.66 27184417
    [Google Scholar]
  25. Giuliano M. Schiff R. Osborne C.K. Trivedi M.V. Biological mechanisms and clinical implications of endocrine resistance in breast cancer. Breast 2011 20 Suppl. 3 S42 S49 10.1016/S0960‑9776(11)70293‑4 22015292
    [Google Scholar]
  26. Paplomata E. O’Regan R. The PI3K/AKT/mTOR pathway in breast cancer: Targets, trials and biomarkers. Ther. Adv. Med. Oncol. 2014 6 4 154 166 10.1177/1758834014530023 25057302
    [Google Scholar]
  27. Miller T.W. Endocrine resistance: What do we know? Am. Soc. Clin. Oncol. Educ. Book 2013 ••• 33 e37 e42 10.14694/EdBook_AM.2013.33.e37 23714450
    [Google Scholar]
  28. Tong C.W.S. Wu M. Cho W.C.S. To K.K.W. Recent advances in the treatment of breast cancer. Front. Oncol. 2018 8 227 10.3389/fonc.2018.00227 29963498
    [Google Scholar]
  29. Chavda V.P. Nalla L.V. Balar P. Bezbaruah R. Apostolopoulos V. Singla R.K. Khadela A. Vora L. Uversky V.N. Advanced phytochemical-based nanocarrier systems for the treatment of breast cancer. Cancers 2023 15 4 1023 10.3390/cancers15041023 36831369
    [Google Scholar]
  30. Meric-Bernstam F. Hung M.C. Advances in targeting human epidermal growth factor receptor-2 signaling for cancer therapy. Clin. Cancer Res. 2006 12 21 6326 6330 10.1158/1078‑0432.CCR‑06‑1732 17085641
    [Google Scholar]
  31. Ménard S. Pupa S.M. Campiglio M. Tagliabue E. Biologic and therapeutic role of HER2 in cancer. Oncogene 2003 22 42 6570 6578 10.1038/sj.onc.1206779 14528282
    [Google Scholar]
  32. Gerber D.E. Targeted therapies: A new generation of cancer treatments. Am. Fam. Physician 2008 77 3 311 319 18297955
    [Google Scholar]
  33. Yadav D. Semwal B.C. Dewangan H.K. Grafting, characterization and enhancement of therapeutic activity of berberine-loaded PEGylated PAMAM dendrimer for cancerous cells. J. Biomater. Sci. Polym. Ed. 2022 14 1 14 36469754
    [Google Scholar]
  34. McCanney J. Winckworth-Prejsnar K. Schatz A.A. Nardi E.A. Dwyer A.J. Lieu C. Biru Y. Carlson R.W. Addressing survivorship in cancer care. J. Natl. Compr. Canc. Netw. 2018 16 7 801 806 10.6004/jnccn.2018.7054 30006422
    [Google Scholar]
  35. Nardin S. Mora E. Varughese F.M. D’Avanzo F. Vachanaram A.R. Rossi V. Saggia C. Rubinelli S. Gennari A. Breast cancer survivorship, quality of life, and late toxicities. Front. Oncol. 2020 10 864 10.3389/fonc.2020.00864 32612947
    [Google Scholar]
  36. Pinto M. Calafiore D. Piccirillo M.C. Costa M. Taskiran O.O. de Sire A. Breast cancer survivorship: The role of rehabilitation according to the international classification of functioning disability and health—a scoping review. Curr. Oncol. Rep. 2022 24 9 1163 1175 10.1007/s11912‑022‑01262‑8 35403973
    [Google Scholar]
  37. Wang B. Rosano J.M. Cheheltani R. Achary M.P. Kiani M.F. Towards a targeted multi-drug delivery approach to improve therapeutic efficacy in breast cancer. Expert Opin. Drug Deliv. 2010 7 10 1159 1173 10.1517/17425247.2010.513968 20738211
    [Google Scholar]
  38. Salemme V. Centonze G. Avalle L. Natalini D. Piccolantonio A. Arina P. Morellato A. Ala U. Taverna D. Turco E. Defilippi P. The role of tumor microenvironment in drug resistance: Emerging technologies to unravel breast cancer heterogeneity. Front. Oncol. 2023 13 1170264 10.3389/fonc.2023.1170264 37265795
    [Google Scholar]
  39. Videira M. Reis R.L. Brito M.A. Deconstructing breast cancer cell biology and the mechanisms of multidrug resistance. Biochim. Biophys. Acta Rev. Cancer 2014 1846 2 312 325 10.1016/j.bbcan.2014.07.011 25080053
    [Google Scholar]
  40. Obidiro O. Battogtokh G. Akala E.O. Triple negative breast cancer treatment options and limitations: Future outlook. Pharmaceutics 2023 15 7 1796 10.3390/pharmaceutics15071796 37513983
    [Google Scholar]
  41. Omar A.M.M.E. AboulWafa O.M. El-Shoukrofy M.S. Amr M.E. Benzoxazole derivatives as new generation of anti-breast cancer agents. Bioorg. Chem. 2020 96 103593 10.1016/j.bioorg.2020.103593 32004897
    [Google Scholar]
  42. Sharma A.N. Dewangan H.K. Upadhyay P.K. Comprehensive review on herbal medicine: Emphasis on current therapy and role of phytoconstituents for cancer treatment. Chem. Biodivers. 2024 21 3 e202301468 10.1002/cbdv.202301468 38206170
    [Google Scholar]
  43. Marwah H. Pant J. Yadav J. Shah K. Dewangan H.K. Biosensor detection of COVID-19 in lung cancer: Hedgehog and mucin signaling insights. Curr. Pharm. Des. 2023 29 43 3442 3457 10.2174/0113816128276948231204111531 38270161
    [Google Scholar]
  44. Gogas H. Dréno B. Larkin J. Demidov L. Stroyakovskiy D. Eroglu Z. Francesco Ferrucci P. Pigozzo J. Rutkowski P. Mackiewicz J. Rooney I. Voulgari A. Troutman S. Pitcher B. Guo Y. Yan Y. Castro M. Mulla S. Flaherty K. Arance A. Cobimetinib plus atezolizumab in BRAFV600 wild-type melanoma: Primary results from the randomized phase III IMspire170 study. Ann. Oncol. 2021 32 3 384 394 10.1016/j.annonc.2020.12.004 33309774
    [Google Scholar]
  45. Sudhesh Dev S. Zainal Abidin S.A. Farghadani R. Othman I. Naidu R. Receptor tyrosine kinases and their signaling pathways as therapeutic targets of curcumin in cancer. Front. Pharmacol. 2021 12 772510 10.3389/fphar.2021.772510 34867402
    [Google Scholar]
  46. Baselga J. Why the epidermal growth factor receptor? The rationale for cancer therapy. Oncologist 2002 7 S4 Suppl. 4 2 8 10.1634/theoncologist.7‑suppl_4‑2 12202782
    [Google Scholar]
  47. Appert-Collin A. Hubert P. Crémel G. Bennasroune A. Role of ErbB receptors in cancer cell migration and invasion. Front. Pharmacol. 2015 6 283 10.3389/fphar.2015.00283 26635612
    [Google Scholar]
  48. Nataraj N.B. Marrocco I. Yarden Y. Roles for growth factors and mutations in metastatic dissemination. Biochem. Soc. Trans. 2021 49 3 1409 1423 10.1042/BST20210048 34100888
    [Google Scholar]
  49. Peng X.H. Karna P. Cao Z. Jiang B.H. Zhou M. Yang L. Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression. J. Biol. Chem. 2006 281 36 25903 25914 10.1074/jbc.M603414200 16847054
    [Google Scholar]
  50. Herbst R.S. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys. 2004 59 2 Suppl. S21 S26 10.1016/j.ijrobp.2003.11.041 15142631
    [Google Scholar]
  51. Ellis LM Epidermal growth factor receptor in tumor angiogenesis. Hematol Oncol Clin North Am. 2004 18 5 1007 1021 10.1016/j.hoc.2004.06.002
    [Google Scholar]
  52. Hah N. Murakami S. Nagari A. Danko C.G. Kraus W.L. Enhancer transcripts mark active estrogen receptor binding sites. Genome Res. 2013 23 8 1210 1223 10.1101/gr.152306.112 23636943
    [Google Scholar]
  53. Trauernicht A.M. Kim S.J. Kim N.H. Boyer T.G. Modulation of estrogen receptor alpha protein level and survival function by DBC-1. Mol. Endocrinol. 2007 21 7 1526 1536 10.1210/me.2007‑0064 17473282
    [Google Scholar]
  54. Fan W. Chang J. Fu P. Endocrine therapy resistance in breast cancer: Current status, possible mechanisms and overcoming strategies. Future Med. Chem. 2015 7 12 1511 1519 10.4155/fmc.15.93 26306654
    [Google Scholar]
  55. Srinivasan S. Nwachukwu J.C. Bruno N.E. Dharmarajan V. Goswami D. Kastrati I. Novick S. Nowak J. Cavett V. Zhou H.B. Boonmuen N. Zhao Y. Min J. Frasor J. Katzenellenbogen B.S. Griffin P.R. Katzenellenbogen J.A. Nettles K.W. Full antagonism of the estrogen receptor without a prototypical ligand side chain. Nat. Chem. Biol. 2017 13 1 111 118 10.1038/nchembio.2236 27870835
    [Google Scholar]
  56. Thomas T. Gallo M. Thomas T. Estrogen receptors as targets for drug development for breast cancer, osteoporosis and cardiovascular diseases. Curr. Cancer Drug Targets 2004 4 6 483 499 10.2174/1568009043332880 15379634
    [Google Scholar]
  57. Xiao T. Li W. Wang X. Xu H. Yang J. Wu Q. Huang Y. Geradts J. Jiang P. Fei T. Chi D. Zang C. Liao Q. Rennhack J. Andrechek E. Li N. Detre S. Dowsett M. Jeselsohn R.M. Liu X.S. Brown M. Estrogen-regulated feedback loop limits the efficacy of estrogen receptor–targeted breast cancer therapy. Proc. Natl. Acad. Sci. USA 2018 115 31 7869 7878 10.1073/pnas.1722617115 29987050
    [Google Scholar]
  58. Choi Y. Estrogen receptor β expression and its clinical implication in breast cancers: Favorable or unfavorable? J. Breast Cancer 2022 25 2 75 93 10.4048/jbc.2022.25.e9 35380018
    [Google Scholar]
  59. Milani A. Geuna E. Mittica G. Valabrega G. Overcoming endocrine resistance in metastatic breast cancer: Current evidence and future directions. World J. Clin. Oncol. 2014 5 5 990 1001 10.5306/wjco.v5.i5.990 25493235
    [Google Scholar]
  60. Palmieri C. Patten D.K. Januszewski A. Zucchini G. Howell S.J. Breast cancer: Current and future endocrine therapies. Mol. Cell. Endocrinol. 2014 382 1 695 723 10.1016/j.mce.2013.08.001 23933149
    [Google Scholar]
  61. Tryfonidis K. Zardavas D. Katzenellenbogen B.S. Piccart M. Endocrine treatment in breast cancer: Cure, resistance and beyond. Cancer Treat. Rev. 2016 50 68 81 10.1016/j.ctrv.2016.08.008 27643748
    [Google Scholar]
  62. Sharma A.N. Upadhyay P.K. Dewangan H.K. Dual combination of resveratrol and pterostilbene aqueous core nanocapsules for integrated prostate cancer targeting. Ther. Deliv. 2024 15 9 685 698 10.1080/20415990.2024.2380239 39129676
    [Google Scholar]
  63. Anderson A.M. Ragan M.A. Palmitoylation: A protein S-acylation with implications for breast cancer. NPJ Breast Cancer 2016 2 1 16028 10.1038/npjbcancer.2016.28 28721385
    [Google Scholar]
  64. Resh M.D. Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci. STKE 2006 2006 359 re14 10.1126/stke.3592006re14 17077383
    [Google Scholar]
  65. Jeselsohn R. Buchwalter G. De Angelis C. Brown M. Schiff R. ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat. Rev. Clin. Oncol. 2015 12 10 573 583 10.1038/nrclinonc.2015.117 26122181
    [Google Scholar]
  66. Sinn B.V. Fu C. Lau R. Litton J. Tsai T.H. Murthy R. Tam A. Andreopoulou E. Gong Y. Murthy R. Gould R. Zhang Y. King T.A. Viale A. Andrade V. Giri D. Salgado R. Laios I. Sotiriou C. Marginean E.C. Kwiatkowski D.N. Layman R.M. Booser D. Hatzis C. Vicente Valero V. Fraser Symmans W. SETER/PR: A robust 18-gene predictor for sensitivity to endocrine therapy for metastatic breast cancer. NPJ Breast Cancer 2019 5 1 16 10.1038/s41523‑019‑0111‑0 31231679
    [Google Scholar]
  67. Lim E. Tarulli G. Portman N. Hickey T.E. Tilley W.D. Palmieri C. Pushing estrogen receptor around in breast cancer. Endocr. Relat. Cancer 2016 23 12 T227 T241 10.1530/ERC‑16‑0427 27729416
    [Google Scholar]
  68. Spinelli M. Fusco S. Grassi C. Nutrient-dependent changes of protein palmitoylation: Impact on nuclear enzymes and regulation of gene expression. Int. J. Mol. Sci. 2018 19 12 3820 10.3390/ijms19123820 30513609
    [Google Scholar]
  69. Plati J. Bucur O. Khosravi-Far R. Apoptotic cell signaling in cancer progression and therapy. Integr. Biol. 2011 3 4 279 296 10.1039/c0ib00144a 21340093
    [Google Scholar]
  70. Adams J. Cory S. Bcl-2-regulated apoptosis: Mechanism and therapeutic potential. Curr. Opin. Immunol. 2007 19 5 488 496 10.1016/j.coi.2007.05.004 17629468
    [Google Scholar]
  71. Hartman M.L. Czyz M. BCL-w: apoptotic and non-apoptotic role in health and disease. Cell Death Dis. 2020 11 4 260 10.1038/s41419‑020‑2417‑0 32317622
    [Google Scholar]
  72. Cloete I Smith V Jackson R Pepper A Pepper C Dyer M P1252: Predicting the response of dlbcl cells to BH3-Mimetics using systems biology HemaSphere 2022 6 1137 1138 10.1097/01.HS9.0000847872.98226.ce
    [Google Scholar]
  73. Han Z. Liang J. Li Y. He J. Drugs and clinical approaches targeting the antiapoptotic protein: A review. BioMed Res. Int. 2019 2019 1 6 10.1155/2019/1212369 31662966
    [Google Scholar]
  74. Nakhjavani M. Shigdar S. Natural blockers of PD-1/PD-L1 interaction for the immunotherapy of triple-negative breast cancer-brain metastasis. Cancers 2022 14 24 6258 10.3390/cancers14246258 36551742
    [Google Scholar]
  75. Sharma N. Bhati A. Aggarwal S. Shah K. Dewangan H.K. PARP pioneers: Using BRCA1/2 mutation-targeted inhibition to revolutionize breast cancer treatment. Curr. Pharm. Des. 2024 10.2174/0113816128322894241004051814 39421986
    [Google Scholar]
  76. El-Sahli S. Hua K. Sulaiman A. Chambers J. Li L. Farah E. McGarry S. Liu D. Zheng P. Lee S.H. Cui J. Ekker M. Côté M. Alain T. Li X. D’Costa V.M. Wang L. Gadde S. A triple-drug nanotherapy to target breast cancer cells, cancer stem cells, and tumor vasculature. Cell Death Dis. 2021 12 1 8 10.1038/s41419‑020‑03308‑w 33414428
    [Google Scholar]
  77. Xu J. Dong X. Huang D.C.S. Xu P. Zhao Q. Chen B. Current advances and future strategies for BCL-2 inhibitors: Potent weapons against cancers. Cancers 2023 15 20 4957 10.3390/cancers15204957 37894324
    [Google Scholar]
  78. Guimaraes D.P. Hainaut P. TP53: A key gene in human cancer. Biochimie 2002 84 1 83 93 10.1016/S0300‑9084(01)01356‑6 11900880
    [Google Scholar]
  79. Brady C.A. Attardi L.D. p53 at a glance. J. Cell Sci. 2010 123 15 2527 2532 10.1242/jcs.064501 20940128
    [Google Scholar]
  80. Liebermann D.A. Hoffman B. Vesely D. p53 induced growth arrest versus apoptosis and its modulation by survival cytokines. Cell Cycle 2007 6 2 166 170 10.4161/cc.6.2.3789 17264673
    [Google Scholar]
  81. Helton E.S. Chen X. p53 modulation of the DNA damage response. J. Cell. Biochem. 2007 100 4 883 896 10.1002/jcb.21091 17031865
    [Google Scholar]
  82. Aubrey B.J. Kelly G.L. Janic A. Herold M.J. Strasser A. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 2018 25 1 104 113 10.1038/cdd.2017.169 29149101
    [Google Scholar]
  83. Perri F. Pisconti S. Della Vittoria Scarpati G. P53 mutations and cancer: A tight linkage. Ann. Transl. Med. 2016 4 24 522 10.21037/atm.2016.12.40 28149884
    [Google Scholar]
  84. Olivier M. Hollstein M. Hainaut P. TP53 mutations in human cancers: Origins, consequences, and clinical use. Cold Spring Harb. Perspect. Biol. 2010 2 1 a001008 10.1101/cshperspect.a001008 20182602
    [Google Scholar]
  85. Kato S. Han S.Y. Liu W. Otsuka K. Shibata H. Kanamaru R. Ishioka C. Understanding the function–structure and function–mutation relationships of p53 tumor suppressor protein by high-resolution missense mutation analysis. Proc. Natl. Acad. Sci. USA 2003 100 14 8424 8429 10.1073/pnas.1431692100 12826609
    [Google Scholar]
  86. Muller P.A.J. Vousden K.H. Mutant p53 in cancer: New functions and therapeutic opportunities. Cancer Cell 2014 25 3 304 317 10.1016/j.ccr.2014.01.021 24651012
    [Google Scholar]
  87. Blandino G. Di Agostino S. New therapeutic strategies to treat human cancers expressing mutant p53 proteins. J. Exp. Clin. Cancer Res. 2018 37 1 30 10.1186/s13046‑018‑0705‑7 29448954
    [Google Scholar]
  88. Silwal-Pandit L. Langerød A. Børresen-Dale A.L. TP53 mutations in breast and ovarian cancer. Cold Spring Harb. Perspect. Med. 2017 7 1 a026252 10.1101/cshperspect.a026252 27815305
    [Google Scholar]
  89. Pan X. Ji X. Zhang R. Zhou Z. Zhong Y. Peng W. Sun N. Xu X. Xia L. Li P. Lu J. Tu J. Landscape of somatic mutations in gastric cancer assessed using next‑generation sequencing analysis. Oncol. Lett. 2018 16 4 4863 4870 10.3892/ol.2018.9314 30250552
    [Google Scholar]
  90. Marques M.A. Andrade G.C. Silva J.L. de Oliveira G.A.P. Protein of a thousand faces: The tumor-suppressive and oncogenic responses of p53. Front. Mol. Biosci. 2022 9 944955 10.3389/fmolb.2022.944955 36090037
    [Google Scholar]
  91. Kleibl Z. Kristensen V.N. Women at high risk of breast cancer: Molecular characteristics, clinical presentation and management. Breast 2016 28 136 144 10.1016/j.breast.2016.05.006 27318168
    [Google Scholar]
  92. Liu Q. Yu S. Zhao W. Qin S. Chu Q. Wu K. EGFR-TKIs resistance via EGFR-independent signaling pathways. Mol. Cancer 2018 17 1 53 10.1186/s12943‑018‑0793‑1 29455669
    [Google Scholar]
  93. Brett J.O. Spring L.M. Bardia A. Wander S.A. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021 23 1 85 10.1186/s13058‑021‑01462‑3 34392831
    [Google Scholar]
  94. Rodriguez-Lara V. Hernandez-Martinez J.M. Arrieta O. Influence of estrogen in non-small cell lung cancer and its clinical implications. J. Thorac. Dis. 2018 10 1 482 497 10.21037/jtd.2017.12.61 29600083
    [Google Scholar]
  95. Wei H. Wang H. Wang G. Qu L. Jiang L. Dai S. Chen X. Zhang Y. Chen Z. Li Y. Guo M. Chen Y. Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity. Nat. Commun. 2023 14 1 4300 10.1038/s41467‑023‑40087‑2 37463921
    [Google Scholar]
  96. Pant J. Mittal P. Singh L. Marwah H. Evolving strategies in NSCLC care: Targeted therapies, biomarkers, predictive models, and patient management. Curr. Pharmacogenomics Person. Med. 2023 20 3 146 164 10.2174/0118756921301200240427053840
    [Google Scholar]
  97. Kawiak A. Kostecka A. Regulation of Bcl-2 family proteins in estrogen receptor-positive breast cancer and their implications in endocrine therapy. Cancers 2022 14 2 279 10.3390/cancers14020279 35053443
    [Google Scholar]
  98. Lok S.W. Whittle J.R. Vaillant F. Teh C.E. Lo L.L. Policheni A.N. Bergin A.R.T. Desai J. Ftouni S. Gandolfo L.C. Liew D. Liu H.K. Mann G.B. Moodie K. Murugasu A. Pal B. Roberts A.W. Rosenthal M.A. Shackleton K. Silva M.J. Siow Z.R. Smyth G.K. Taylor L. Travers A. Yeo B. Yeung M.M. Bujak A.Z. Dawson S.J. Gray D.H.D. Visvader J.E. Lindeman G.J. A phase Ib dose-escalation and expansion study of the BCL2 inhibitor venetoclax combined with Tamoxifen in ER and BCL2–positive metastatic breast cancer. Cancer Discov. 2019 9 3 354 369 10.1158/2159‑8290.CD‑18‑1151 30518523
    [Google Scholar]
  99. Zebisch A. Czernilofsky A. Keri G. Smigelskaite J. Sill H. Troppmair J. Signaling through RAS-RAF-MEK-ERK: From basics to bedside. Curr. Med. Chem. 2007 14 5 601 623 10.2174/092986707780059670 17346150
    [Google Scholar]
  100. Zhou B.P. Li Y. Hung M.C. HER-2/Neu signaling and therapeutic approaches in breast cancer. Breast Dis. 2002 15 1 13 24 10.3233/BD‑2002‑15103 15687642
    [Google Scholar]
  101. Lux M.P. Fasching P.A. Schrauder M.G. Hein A. Jud S.M. Rauh C. Beckmann M.W. The PI3K Pathway: Background and treatment approaches. Breast Care 2016 11 6 398 404 10.1159/000453133 28228706
    [Google Scholar]
  102. Jiang N. Saba N.F. Chen Z.G. Advances in targeting HER3 as an anticancer therapy. Chemother. Res. Pract. 2012 2012 1 9 10.1155/2012/817304 23198146
    [Google Scholar]
  103. Hassan B. Akcakanat A. Holder A.M. Meric-Bernstam F. Targeting the PI3-kinase/Akt/mTOR signaling pathway. Surg. Oncol. Clin. N. Am. 2013 22 4 641 664 10.1016/j.soc.2013.06.008 24012393
    [Google Scholar]
  104. Benvenuti S. Sartore-Bianchi A. Di Nicolantonio F. Zanon C. Moroni M. Veronese S. Siena S. Bardelli A. Oncogenic activation of the RAS/RAF signaling pathway impairs the response of metastatic colorectal cancers to anti-epidermal growth factor receptor antibody therapies. Cancer Res. 2007 67 6 2643 2648 10.1158/0008‑5472.CAN‑06‑4158 17363584
    [Google Scholar]
  105. Pant J. Singh L. Mittal P. Kumar N. Valencene as a novel potential downregulator of THRB in NSCLC: network pharmacology, molecular docking, molecular dynamics simulation, ADMET analysis, and in vitro analysis. Mol. Divers. 2024 10.1007/s11030‑024‑11008‑2 39425858
    [Google Scholar]
  106. Porta C. Paglino C. Mosca A. Targeting PI3K/Akt/mTOR signaling in cancer. Front. Oncol. 2014 4 64 10.3389/fonc.2014.00064 24782981
    [Google Scholar]
  107. Ci Y. Qiao J. Han M. Molecular mechanisms and metabolomics of natural polyphenols interfering with breast cancer metastasis. Molecules 2016 21 12 1634 10.3390/molecules21121634 27999314
    [Google Scholar]
  108. Sha S. Yuan D. Liu Y. Han B. Zhong N. Liu Z. Targeting long non-coding RNA DANCR inhibits triple negative breast cancer progression. Biol. Open 2017 6 9 bio.023135 10.1242/bio.023135 28760736
    [Google Scholar]
  109. Vivekanandhan S. Mukhopadhyay D. Genetic status of KRAS influences Transforming Growth Factor-beta (TGF-β) signaling: An insight into Neuropilin-1 (NRP1) mediated tumorigenesis. Semin. Cancer Biol. 2019 54 72 79 10.1016/j.semcancer.2018.01.014 29409705
    [Google Scholar]
  110. Lebert J.M. Lester R. Powell E. Seal M. McCarthy J. Advances in the systemic treatment of triple-negative breast cancer. Curr. Oncol. 2018 25 11 Suppl. 1 142 150 10.3747/co.25.3954 29910657
    [Google Scholar]
  111. Yang X.H. Ai X. Cunningham J. Computational prognostic indicators for breast cancer. Cancer Manag. Res. 2014 6 301 312 10.2147/CMAR.S46483 25050076
    [Google Scholar]
  112. Geyer C.E. Forster J. Lindquist D. Chan S. Romieu C.G. Pienkowski T. Jagiello-Gruszfeld A. Crown J. Chan A. Kaufman B. Skarlos D. Campone M. Davidson N. Berger M. Oliva C. Rubin S.D. Stein S. Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N. Engl. J. Med. 2006 355 26 2733 2743 10.1056/NEJMoa064320 17192538
    [Google Scholar]
  113. Britten C.D. Finn R.S. Bosserman L.D. Wong S.G. Press M.F. Malik M. Lum B.L. Slamon D.J. A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: A dual ErbB targeted approach. Clin. Breast Cancer 2009 9 1 16 22 10.3816/CBC.2009.n.003 19299235
    [Google Scholar]
  114. Hickish T. Mehta A. Liu M.C. Huang C.S. Arora R.S. Chang Y.C. Yang Y. Vladimirov V. Jain M. Tsang J. Pemberton K. Sadrolhefazi B. Jin X. Tseng L.M. Afatinib alone and in combination with vinorelbine or paclitaxel, in patients with HER2-positive breast cancer who failed or progressed on prior trastuzumab and/or lapatinib (LUX-Breast 2): An open-label, multicenter, phase II trial. Breast Cancer Res. Treat. 2022 192 3 593 602 10.1007/s10549‑021‑06449‑4 35138529
    [Google Scholar]
  115. Liao W.S. Ho Y. Lin Y.W. Naveen Raj E. Liu K.K. Chen C. Zhou X.Z. Lu K.P. Chao J.I. Targeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocomposite. Acta Biomater. 2019 86 395 405 10.1016/j.actbio.2019.01.025 30660004
    [Google Scholar]
  116. Takaoka T. Kimura T. Shimoyama R. Kawamoto S. Sakamoto K. Goda F. Miyamoto H. Negoro Y. Tsuji A. Yoshizaki K. Goji T. Kitamura S. Yano H. Okamoto K. Kimura M. Okahisa T. Muguruma N. Niitsu Y. Takayama T. Panitumumab in combination with irinotecan plus S-1 (IRIS) as second-line therapy for metastatic colorectal cancer. Cancer Chemother. Pharmacol. 2016 78 2 397 403 10.1007/s00280‑016‑3096‑5 27342247
    [Google Scholar]
  117. Traynor A.M. Schiller J.H. Stabile L.P. Kolesar J.M. Eickhoff J.C. Dacic S. Hoang T. Dubey S. Marcotte S.M. Siegfried J.M. Pilot study of gefitinib and fulvestrant in the treatment of post-menopausal women with advanced non-small cell lung cancer. Lung Cancer 2009 64 1 51 59 10.1016/j.lungcan.2008.07.002 18701186
    [Google Scholar]
  118. Slamon D.J. Diéras V. Rugo H.S. Harbeck N. Im S.A. Gelmon K.A. Lipatov O.N. Walshe J.M. Martin M. Chavez-MacGregor M. Bananis E. Gauthier E. Lu D.R. Kim S. Finn R.S. Overall survival with Palbociclib plus letrozole in advanced breast cancer. J. Clin. Oncol. 2024 42 9 994 1000 10.1200/JCO.23.00137 38252901
    [Google Scholar]
  119. Tolaney S.M. Beeram M. Beck J.T. Conlin A. Dees E.C. Puhalla S.L. Rexer B.N. Burris H.A. III Jhaveri K. Helsten T. Becerra C. Kalinsky K. Moore K.N. Manuel A.M. Lithio A. Price G.L. Chapman S.C. Litchfield L.M. Goetz M.P. Abemaciclib in combination with endocrine therapy for patients with hormone receptor-positive, HER2-negative metastatic breast cancer: A phase 1b study. Front. Oncol. 2022 11 810023 10.3389/fonc.2021.810023 35223458
    [Google Scholar]
  120. Mo H. Renna C.E. Moore H.C.F. Abraham J. Kruse M.L. Montero A.J. LeGrand S.B. Wang L. Budd G.T. Real-world outcomes of everolimus and exemestane for the treatment of metastatic hormone receptor-positive breast cancer in patients previously treated with CDK4/6 inhibitors. Clin. Breast Cancer 2022 22 2 143 148 10.1016/j.clbc.2021.10.002 34740541
    [Google Scholar]
  121. André F. Ciruelos E.M. Juric D. Loibl S. Campone M. Mayer I.A. Rubovszky G. Yamashita T. Kaufman B. Lu Y.S. Inoue K. Pápai Z. Takahashi M. Ghaznawi F. Mills D. Kaper M. Miller M. Conte P.F. Iwata H. Rugo H.S. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2–negative advanced breast cancer: Final overall survival results from SOLAR-1. Ann. Oncol. 2021 32 2 208 217 10.1016/j.annonc.2020.11.011 33246021
    [Google Scholar]
  122. Shiba E. Yamashita H. Kurebayashi J. Noguchi S. Iwase H. Ohashi Y. Sasai K. Fujimoto T. A randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-months depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer. Breast Cancer 2016 23 3 499 509 10.1007/s12282‑015‑0593‑z 25655898
    [Google Scholar]
  123. Im S.A. Mukai H. Park I.H. Masuda N. Shimizu C. Kim S.B. Im Y.H. Ohtani S. Huang Bartlett C. Lu D.R. Iyer S. Mori Y. Mori A. Gauthier E. Finn R.S. Toi M. Palbociclib plus letrozole as first-line therapy in postmenopausal asian women with metastatic breast cancer: Results from the phase III, randomized PALOMA-2 study. J. Glob. Oncol. 2019 5 5 1 19 10.1200/JGO.18.00173 31125276
    [Google Scholar]
  124. Marczyk M. Patwardhan G.A. Zhao J. Qu R. Li X. Wali V.B. Gupta A.K. Pillai M.M. Kluger Y. Yan Q. Hatzis C. Pusztai L. Gunasekharan V. Multi-omics investigation of innate navitoclax resistance in triple-negative breast cancer cells. Cancers 2020 12 9 2551 10.3390/cancers12092551 32911681
    [Google Scholar]
  125. Schwartz-Roberts J.L. Shajahan A.N. Cook K.L. Wärri A. Abu-Asab M. Clarke R. GX15-070 (obatoclax) induces apoptosis and inhibits cathepsin D- and L-mediated autophagosomal lysis in antiestrogen-resistant breast cancer cells. Mol. Cancer Ther. 2013 12 4 448 459 10.1158/1535‑7163.MCT‑12‑0617 23395885
    [Google Scholar]
  126. Deng J. Letai A. Priming BCL-2 to kill: The combination therapy of tamoxifen and ABT-199 in ER+ breast cancer. Breast Cancer Res. 2013 15 5 317 10.1186/bcr3568 24172207
    [Google Scholar]
  127. Xiong J. Li J. Yang Q. Wang J. Su T. Zhou S. Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer. Breast Cancer Res. 2017 19 1 27 10.1186/s13058‑017‑0818‑5 28274247
    [Google Scholar]
  128. Pan M. Solozobova V. Kuznik N.C. Jung N. Gräßle S. Gourain V. Heneka Y.M. Cramer von Clausbruch C.A. Fuhr O. Munuganti R.S.N. Maddalo D. Blattner C. Neeb A. Sharp A. Cato L. Weiss C. Jeselsohn R.M. Orian-Rousseau V. Bräse S. Cato A.C.B. Identification of an imidazopyridine-based compound as an oral selective estrogen receptor degrader for breast cancer therapy. Cancer Res. Commun. 2023 3 7 1378 1396 10.1158/2767‑9764.CRC‑23‑0111 37520743
    [Google Scholar]
  129. Emma Hitt Nichols P. More approaches are emerging in TP53-mutated AML. Targeted Therapies in Oncology. 2023 11 65
    [Google Scholar]
  130. Menichini P. Monti P. Speciale A. Cutrona G. Matis S. Fais F. Taiana E. Neri A. Bomben R. Gentile M. Gattei V. Ferrarini M. Morabito F. Fronza G. Antitumor effects of PRIMA-1 and PRIMA-1Met (APR246) in hematological malignancies: Still a mutant P53-Dependent affair? Cells 2021 10 1 98 10.3390/cells10010098 33430525
    [Google Scholar]
  131. Synnott NC O'Connell DJ Crown J Duffy MJ Targeting mutant p53 with COTI-2: A new approach for the treatment of patients with triple-negative breast cancer?. JCO 2018 36 e13121 e13121 10.1200/JCO.2018.36.15_suppl.e13121
    [Google Scholar]
  132. Leijen S. van Geel R.M.J.M. Pavlick A.C. Tibes R. Rosen L. Razak A.R.A. Lam R. Demuth T. Rose S. Lee M.A. Freshwater T. Shumway S. Liang L.W. Oza A.M. Schellens J.H.M. Shapiro G.I. Phase I study evaluating WEE1 inhibitor AZD1775 as monotherapy and in combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors. J. Clin. Oncol. 2016 34 36 4371 4380 10.1200/JCO.2016.67.5991 27601554
    [Google Scholar]
  133. Wang Z. Hu H. Heitink L. Rogers K. You Y. Tan T. Suen C.L.W. Garnham A. Chen H. Lieschke E. Diepstraten S.T. Chang C. Chen T. Moujalled D. Sutherland K. Lessene G. Sieber O.M. Visvader J. Kelly G.L. Strasser A. The anti-cancer agent APR-246 can activate several programmed cell death processes to kill malignant cells. Cell Death Differ. 2023 30 4 1033 1046 10.1038/s41418‑023‑01122‑3 36739334
    [Google Scholar]
  134. Nagourney A.J. Gipoor J.B. Evans S.S. D’Amora P. Duesberg M.S. Bernard P.J. Francisco F. Nagourney R.A. Therapeutic targeting of P53: A comparative analysis of APR-246 and COTI-2 in human tumor primary culture 3-D explants. Genes 2023 14 3 747 10.3390/genes14030747 36981018
    [Google Scholar]
  135. Agrawal L. Engel K.B. Greytak S.R. Moore H.M. Understanding preanalytical variables and their effects on clinical biomarkers of oncology and immunotherapy. Semin. Cancer Biol. 2018 52 Pt 2 26 38 10.1016/j.semcancer.2017.12.008 29258857
    [Google Scholar]
  136. Zheng Y. Study design considerations for cancer biomarker discoveries. J. Appl. Lab. Med. 2018 3 2 282 289 10.1373/jalm.2017.025809 30828695
    [Google Scholar]
  137. McShane L.M. Altman D.G. Sauerbrei W. Taube S.E. Gion M. Clark G.M. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br. J. Cancer 2005 93 4 387 391 10.1038/sj.bjc.6602678 16106245
    [Google Scholar]
  138. Moore H.M. Kelly A.B. Jewell S.D. McShane L.M. Clark D.P. Greenspan R. Hayes D.F. Hainaut P. Kim P. Mansfield E. Potapova O. Riegman P. Rubinstein Y. Seijo E. Somiari S. Watson P. Weier H.U. Zhu C. Vaught J. Biospecimen reporting for improved study quality (BRISQ). J. Proteome Res. 2011 10 8 3429 3438 10.1021/pr200021n 21574648
    [Google Scholar]
  139. Ahmad A. Imran M. Ahsan H. Biomarkers as biomedical bioindicators: Approaches and techniques for the detection, analysis, and validation of novel biomarkers of diseases. Pharmaceutics 2023 15 6 1630 10.3390/pharmaceutics15061630 37376078
    [Google Scholar]
  140. Gerdes H. Casado P. Dokal A. Hijazi M. Akhtar N. Osuntola R. Rajeeve V. Fitzgibbon J. Travers J. Britton D. Khorsandi S. Cutillas P.R. Drug ranking using machine learning systematically predicts the efficacy of anti-cancer drugs. Nat. Commun. 2021 12 1 1850 10.1038/s41467‑021‑22170‑8 33767176
    [Google Scholar]
  141. Schneble E.J. Graham L.J. Shupe M.P. Flynt F.L. Banks K.P. Kirkpatrick A.D. Nissan A. Henry L. Stojadinovic A. Shumway N.M. Avital I. Peoples G.E. Setlik R.F. Current approaches and challenges in early detection of breast cancer recurrence. J. Cancer 2014 5 4 281 290 10.7150/jca.8016 24790656
    [Google Scholar]
  142. Tsimberidou A.M. Eggermont A.M.M. Schilsky R.L. Precision cancer medicine: The future is now, only better. Am. Soc. Clin. Oncol. Educ. Book 2014 ••• 34 61 69 10.14694/EdBook_AM.2014.34.61 24857061
    [Google Scholar]
  143. Venook A.P. Arcila M.E. Benson A.B. III Berry D.A. Camidge D.R. Carlson R.W. Choueiri T.K. Guild V. Kalemkerian G.P. Kurzrock R. Lovly C.M. McKee A.E. Morgan R.J. Olszanski A.J. Redman M.W. Stearns V. McClure J. Birkeland M.L. NCCN Working Group report: designing clinical trials in the era of multiple biomarkers and targeted therapies. J. Natl. Compr. Canc. Netw. 2014 12 11 1629 1649 10.6004/jnccn.2014.0161 25361808
    [Google Scholar]
  144. Costello J.C. Heiser L.M. Georgii E. Gönen M. Menden M.P. Wang N.J. Bansal M. Ammad-ud-din M. Hintsanen P. Khan S.A. Mpindi J.P. Kallioniemi O. Honkela A. Aittokallio T. Wennerberg K. Collins J.J. Gallahan D. Singer D. Saez-Rodriguez J. Kaski S. Gray J.W. Stolovitzky G. A community effort to assess and improve drug sensitivity prediction algorithms. Nat. Biotechnol. 2014 32 12 1202 1212 10.1038/nbt.2877 24880487
    [Google Scholar]
  145. Jagosky M. Tan A.R. Combination of pertuzumab and trastuzumab in the treatment of HER2-positive early breast cancer: A review of the emerging clinical data. Breast Cancer 2021 13 393 407 10.2147/BCTT.S176514 34163239
    [Google Scholar]
  146. Awada A. Colomer R. Inoue K. Bondarenko I. Badwe R.A. Demetriou G. Lee S.C. Mehta A.O. Kim S.B. Bachelot T. Goswami C. Deo S. Bose R. Wong A. Xu F. Yao B. Bryce R. Carey L.A. Neratinib plus paclitaxel vs trastuzumab plus paclitaxel in previously untreated metastatic ERBB2-positive breast cancer. JAMA Oncol. 2016 2 12 1557 1564 10.1001/jamaoncol.2016.0237 27078022
    [Google Scholar]
  147. Murthy R.K. Loi S. Okines A. Paplomata E. Hamilton E. Hurvitz S.A. Lin N.U. Borges V. Abramson V. Anders C. Bedard P.L. Oliveira M. Jakobsen E. Bachelot T. Shachar S.S. Müller V. Braga S. Duhoux F.P. Greil R. Cameron D. Carey L.A. Curigliano G. Gelmon K. Hortobagyi G. Krop I. Loibl S. Pegram M. Slamon D. Palanca-Wessels M.C. Walker L. Feng W. Winer E.P. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N. Engl. J. Med. 2020 382 7 597 609 10.1056/NEJMoa1914609 31825569
    [Google Scholar]
  148. Rugo H.S. Im S.A. Cardoso F. Cortés J. Curigliano G. Musolino A. Pegram M.D. Wright G.S. Saura C. Escrivá-de-Romaní S. De Laurentiis M. Levy C. Brown-Glaberman U. Ferrero J.M. de Boer M. Kim S.B. Petráková K. Yardley D.A. Freedman O. Jakobsen E.H. Kaufman B. Yerushalmi R. Fasching P.A. Nordstrom J.L. Bonvini E. Koenig S. Edlich S. Hong S. Rock E.P. Gradishar W.J. Efficacy of margetuximab vs trastuzumab in patients with pretreated ERBB2-positive advanced breast cancer. JAMA Oncol. 2021 7 4 573 584 10.1001/jamaoncol.2020.7932 33480963
    [Google Scholar]
  149. Finn R.S. Martin M. Rugo H.S. Jones S. Im S.A. Gelmon K. Harbeck N. Lipatov O.N. Walshe J.M. Moulder S. Gauthier E. Lu D.R. Randolph S. Diéras V. Slamon D.J. Palbociclib and letrozole in advanced breast cancer. N. Engl. J. Med. 2016 375 20 1925 1936 10.1056/NEJMoa1607303 27959613
    [Google Scholar]
  150. Cardoso F. Senkus E. Costa A. Papadopoulos E. Aapro M. André F. Harbeck N. Aguilar Lopez B. Barrios C.H. Bergh J. Biganzoli L. Boers-Doets C.B. Cardoso M.J. Carey L.A. Cortés J. Curigliano G. Diéras V. El Saghir N.S. Eniu A. Fallowfield L. Francis P.A. Gelmon K. Johnston S.R.D. Kaufman B. Koppikar S. Krop I.E. Mayer M. Nakigudde G. Offersen B.V. Ohno S. Pagani O. Paluch-Shimon S. Penault-Llorca F. Prat A. Rugo H.S. Sledge G.W. Spence D. Thomssen C. Vorobiof D.A. Xu B. Norton L. Winer E.P. 4th ESO–ESMO international consensus guidelines for advanced breast cancer (ABC 4). Ann. Oncol. 2018 29 8 1634 1657 10.1093/annonc/mdy192 30032243
    [Google Scholar]
  151. Riccardi F. Colantuoni G. Diana A. Mocerino C. Cartenì G. Lauria R. Febbraro A. Nuzzo F. Addeo R. Marano O. Incoronato P. De Placido S. Ciardiello F. Orditura M. Exemestane and Everolimus combination treatment of hormone receptor positive, HER2 negative metastatic breast cancer: A retrospective study of 9 cancer centers in the Campania Region (Southern Italy) focused on activity, efficacy and safety. Mol. Clin. Oncol. 2018 9 3 255 263 10.3892/mco.2018.1672 30155246
    [Google Scholar]
  152. André F. Ciruelos E. Rubovszky G. Campone M. Loibl S. Rugo H.S. Iwata H. Conte P. Mayer I.A. Kaufman B. Yamashita T. Lu Y.S. Inoue K. Takahashi M. Pápai Z. Longin A.S. Mills D. Wilke C. Hirawat S. Juric D. Alpelisib for PIK3CA -Mutated, hormone receptor–positive advanced breast cancer. N. Engl. J. Med. 2019 380 20 1929 1940 10.1056/NEJMoa1813904 31091374
    [Google Scholar]
  153. Tutt A.N.J. Garber J.E. Kaufman B. Viale G. Fumagalli D. Rastogi P. Gelber R.D. de Azambuja E. Fielding A. Balmaña J. Domchek S.M. Gelmon K.A. Hollingsworth S.J. Korde L.A. Linderholm B. Bandos H. Senkus E. Suga J.M. Shao Z. Pippas A.W. Nowecki Z. Huzarski T. Ganz P.A. Lucas P.C. Baker N. Loibl S. McConnell R. Piccart M. Schmutzler R. Steger G.G. Costantino J.P. Arahmani A. Wolmark N. McFadden E. Karantza V. Lakhani S.R. Yothers G. Campbell C. Geyer C.E. Jr Adjuvant olaparib for patients with BRCA1 - or BRCA2 -Mutated breast cancer. N. Engl. J. Med. 2021 384 25 2394 2405 10.1056/NEJMoa2105215 34081848
    [Google Scholar]
  154. Litton J.K. Rugo H.S. Ettl J. Hurvitz S.A. Gonçalves A. Lee K.H. Fehrenbacher L. Yerushalmi R. Mina L.A. Martin M. Roché H. Im Y.H. Quek R.G.W. Markova D. Tudor I.C. Hannah A.L. Eiermann W. Blum J.L. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N. Engl. J. Med. 2018 379 8 753 763 10.1056/NEJMoa1802905 30110579
    [Google Scholar]
  155. Criscitiello C. Viale G. Curigliano G. Goldhirsch A. Profile of buparlisib and its potential in the treatment of breast cancer: Evidence to date. Breast Cancer 2018 10 23 29 10.2147/BCTT.S134641 29430197
    [Google Scholar]
  156. Turner N. Dent R.A. O’Shaughnessy J. Kim S.B. Isakoff S.J. Barrios C. Saji S. Bondarenko I. Nowecki Z. Lian Q. Reilly S.J. Hinton H. Wongchenko M.J. Kovic B. Mani A. Oliveira M. Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: Primary results from cohort B of the IPATunity130 randomized phase 3 trial. Breast Cancer Res. Treat. 2022 191 3 565 576 10.1007/s10549‑021‑06450‑x 34860318
    [Google Scholar]
  157. Schmid P. Adams S. Rugo H.S. Schneeweiss A. Barrios C.H. Iwata H. Diéras V. Hegg R. Im S.A. Shaw Wright G. Henschel V. Molinero L. Chui S.Y. Funke R. Husain A. Winer E.P. Loi S. Emens L.A. Atezolizumab and Nab-Paclitaxel in advanced triple-negative breast cancer. N. Engl. J. Med. 2018 379 22 2108 2121 10.1056/NEJMoa1809615 30345906
    [Google Scholar]
  158. Cortes J. Rugo H.S. Cescon D.W. Im S.A. Yusof M.M. Gallardo C. Lipatov O. Barrios C.H. Perez-Garcia J. Iwata H. Masuda N. Torregroza Otero M. Gokmen E. Loi S. Guo Z. Zhou X. Karantza V. Pan W. Schmid P. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N. Engl. J. Med. 2022 387 3 217 226 10.1056/NEJMoa2202809 35857659
    [Google Scholar]
  159. Loibl S. Schneeweiss A. Huober J. Braun M. Rey J. Blohmer J.U. Furlanetto J. Zahm D.M. Hanusch C. Thomalla J. Jackisch C. Staib P. Link T. Rhiem K. Solbach C. Fasching P.A. Nekljudova V. Denkert C. Untch M. Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response. Ann. Oncol. 2022 33 11 1149 1158 10.1016/j.annonc.2022.07.1940 35961599
    [Google Scholar]
  160. Krop I. Abramson V. Colleoni M. Traina T. Holmes F. Garcia-Estevez L. Hart L. Awada A. Zamagni C. Morris P.G. Schwartzberg L. Chan S. Gucalp A. Biganzoli L. Steinberg J. Sica L. Trudeau M. Markova D. Tarazi J. Zhu Z. O’Brien T. Kelly C.M. Winer E. Yardley D.A. A randomized placebo controlled phase II trial evaluating exemestane with or without enzalutamide in patients with hormone receptor–positive breast cancer. Clin. Cancer Res. 2020 26 23 6149 6157 10.1158/1078‑0432.CCR‑20‑1693 32988969
    [Google Scholar]
  161. Saltzstein D. Sieber P. Morris T. Gallo J. Prevention and management of bicalutamide-induced gynecomastia and breast pain: Randomized endocrinologic and clinical studies with tamoxifen and anastrozole. Prostate Cancer Prostatic Dis. 2005 8 1 75 83 10.1038/sj.pcan.4500782 15685254
    [Google Scholar]
  162. Loriot Y Schuler MH Iyer G Witt O Doi T Qin S Tumor agnostic efficacy and safety of erdafitinib in patients (pts) with advanced solid tumors with prespecified fibroblast growth factor receptor alterations (FGFRalt) in RAGNAR: Interim analysis (IA) results. JCO 2022 40 3007 3007 10.1200/JCO.2022.40.16_suppl.3007
    [Google Scholar]
  163. Musolino A. Campone M. Neven P. Denduluri N. Barrios C.H. Cortes J. Blackwell K. Soliman H. Kahan Z. Bonnefoi H. Squires M. Zhang Y. Deudon S. Shi M.M. André F. Phase II, randomized, placebo-controlled study of dovitinib in combination with fulvestrant in postmenopausal patients with HR+, HER2− breast cancer that had progressed during or after prior endocrine therapy. Breast Cancer Res. 2017 19 1 18 10.1186/s13058‑017‑0807‑8 28183331
    [Google Scholar]
  164. Gupta S. Verma V. Dwarakanath B.S. Emerging concepts in cancer therapy: Mechanisms of resistance. Cancer Rep. 2022 5 12 e1715 10.1002/cnr2.1715 36083019
    [Google Scholar]
  165. Derbal Y. The adaptive complexity of cancer. BioMed Res. Int. 2018 2018 1 14 10.1155/2018/5837235 30627563
    [Google Scholar]
  166. Tyner J.W. Haderk F. Kumaraswamy A. Baughn L.B. Van Ness B. Liu S. Marathe H. Alumkal J.J. Bivona T.G. Chan K.S. Druker B.J. Hutson A.D. Nelson P.S. Sawyers C.L. Willey C.D. Understanding drug sensitivity and tackling resistance in cancer. Cancer Res. 2022 82 8 1448 1460 10.1158/0008‑5472.CAN‑21‑3695 35195258
    [Google Scholar]
  167. Ward R.A. Fawell S. Floc’h N. Flemington V. McKerrecher D. Smith P.D. Challenges and opportunities in cancer drug resistance. Chem. Rev. 2021 121 6 3297 3351 10.1021/acs.chemrev.0c00383 32692162
    [Google Scholar]
  168. Marwah H. Dewangan H.K. Advancements in solid lipid nanoparticles and nanostructured lipid carriers for breast cancer therapy. Curr. Pharm. Des. 2024 30 37 2922 2936 10.2174/0113816128319233240725103706 39150028
    [Google Scholar]
  169. Dewangan H.K. The emerging role of nanosuspensions for drug delivery and stability. Curr. Nanomed. 2021 11 4 213 223 10.2174/2468187312666211222123307
    [Google Scholar]
  170. Dewangan H.K. Rai A. Shah K. Sharma R. A comprehensive review on COVID-19: Emphasis on current vaccination and nanotechnology aspects. Recent Pat. Nanotechnol. 2023 17 4 359 377 10.2174/1872210516666220819104853 35986540
    [Google Scholar]
  171. Dubey R.K. Shukla S. Shah K. Dewangan H.K. A comprehensive review of self-assembly techniques used to fabricate as DNA origami, block copolymers, and colloidal nanostructures. Curr. Nanosci. 2024 20 10.2174/0115734137283662240129073747
    [Google Scholar]
  172. Deepika D. Dewangan H.K. Maurya L. Singh S. Intranasal drug delivery of frovatriptan succinate-loaded polymeric nanoparticles for brain targeting. J. Pharm. Sci. 2019 108 2 851 859 10.1016/j.xphs.2018.07.013 30053555
    [Google Scholar]
  173. Dewangan H.K. Pandey T. Maurya L. Singh S. Rational design and evaluation of HBsAg polymeric nanoparticles as antigen delivery carriers. Int. J. Biol. Macromol. 2018 111 804 812 10.1016/j.ijbiomac.2018.01.073 29343454
    [Google Scholar]
  174. Vanshita Garg A. Dewangan H.K. Recent advances in drug design and delivery across biological barriers using computational models. Lett. Drug Des. Discov. 2022 19 10 865 876 10.2174/1570180819999220204110306
    [Google Scholar]
  175. Vanshita G.A. Shah K. Sharma R. Dewangan H.K. Review: Recent advances of nanotechnology in brain targeting. Curr. Nanosci. 2022 19 350 361 10.2174/1570180819999220204110306
    [Google Scholar]
/content/journals/ccdt/10.2174/0115680096366956250314043513
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Synergistic Targeting of EGFR, ESR1, BCL2, and TP53 Pathways: A 
Multi-Pronged Approach for Advanced Breast Cancer Therapy
Bentham Science Publishers ; https://doi.org/10.2174/0115680096366956250314043513
/content/journals/ccdt/10.2174/0115680096366956250314043513
/content/journals/ccdt/10.2174/0115680096366956250314043513
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  • Article Type:     Review Article
Keywords: BCL2 ; EGFR ; TP53 ; Breast cancer ; ESR1 ; heterogeneity

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