Skip to content
2000
image of Targeting Cell Signalling Pathways with New Small Molecules in 
Inflammation and Cancer

Abstract

In the treatment of cancer and inflammation, small molecules become powerful therapeutic tools that provide new therapeutic approaches with improved efficacy and fewer side effects. This review offers a thorough summary of current developments in small-molecule drugs that target cancer and inflammatory pathways. Specifically, inhibition of phosphodiesterase-4 (PDE4) and COX receptors have demonstrated potential in the field of inflammation to help mitigate a variety of inflammatory disorders. We examine the structural design, mechanism of action, and therapeutic potential of innovative small compounds that inhibit or alter these pathways. Significant attention is placed on the dual anti-inflammatory and anti-cancer properties of these substances. The evaluation emphasizes preclinical and clinical data, revealing the most promising candidates under development. In summary, the precise manipulation of cellular signalling pathways by small compounds constitutes a dynamic domain with the capacity to revolutionize therapeutic approaches for inflammation and cancer. Ongoing investigation of these chemicals is essential for the advancement of safer and more efficacious therapies.

Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266360926250509040743
2025-05-12
2025-12-09
Loading full text...

Full text loading...

References

  1. Ni Y. Zhu R. Kokot S. Competitive binding of small molecules with biopolymers: A fluorescence spectroscopy and chemometrics study of the interaction of aspirin and ibuprofen with BSA. Analyst (Lond.) 2011 136 22 4794 4801 10.1039/c1an15550d 21952617
    [Google Scholar]
  2. Vane J. R. Aspirin and other anti-inflammatory drugs. Thorax 2000 55 2 S3 10.1136/thorax.55.suppl_2.S3
    [Google Scholar]
  3. Vane J.R. Botting R.M. The mechanism of action of aspirin. Thromb. Res. 2003 110 5-6 255 258 10.1016/S0049‑3848(03)00379‑7 14592543
    [Google Scholar]
  4. Paez Espinosa E.V. Murad J.P. Khasawneh F.T. Aspirin: Pharmacology and clinical applications. Thrombosis 2012 2012 1 15 10.1155/2012/173124 22195279
    [Google Scholar]
  5. Rao P.P.N. Kabir S.N. Mohamed T. Nonsteroidal anti-inflammatory drugs (NSAIDs): Progress in small molecule drug development. Pharmaceuticals 2010 3 5 1530 1549 10.3390/ph3051530 27713316
    [Google Scholar]
  6. Hawkey C.J. COX-1 and COX-2 inhibitors. Best Pract. Res. Clin. Gastroenterol. 2001 15 5 801 820 10.1053/bega.2001.0236 11566042
    [Google Scholar]
  7. Rainsford K.D. Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Am. J. Med. 1999 107 6 27 35 10.1016/S0002‑9343(99)00365‑4 10628591
    [Google Scholar]
  8. Marsico F. Paolillo S. Filardi P.P. NSAIDs and cardiovascular risk. J. Cardiovasc. Med. (Hagerstown) 2017 18 1 e40 e43 Special Issue on The State of the Art for the Practicing Cardiologist: The 2016 Conoscere E Curare Il Cuore (CCC) Proceedings from the CLI Foundation. 10.2459/JCM.0000000000000443 27652819
    [Google Scholar]
  9. de Leval X. Julémont F. Delarge J. Pirotte B. Dogné J-M. New trends in dual 5-LOX/COX inhibition. Curr. Med. Chem. 2002 9 9 941 962 10.2174/0929867024606713 11966455
    [Google Scholar]
  10. de Gaetano G. Donati M.B. Cerletti C. Prevention of thrombosis and vascular inflammation: benefits and limitations of selective or combined COX-1, COX-2 and 5-LOX inhibitors. Trends Pharmacol. Sci. 2003 24 5 245 252 10.1016/S0165‑6147(03)00077‑4 12767724
    [Google Scholar]
  11. Rao P. Knaus E.E. Evolution of nonsteroidal anti-inflammatory drugs (NSAIDs): cyclooxygenase (COX) inhibition and beyond. J. Pharm. Pharm. Sci. 2008 11 2 81 10.18433/J3T886 19203472
    [Google Scholar]
  12. Mandal S.K. A review on nonsteroidal anti-inflammatory drugs (NSAIDs). Pharmawave. 2013 6 12 22
    [Google Scholar]
  13. Vane J.R. Bakhle Y.S. Botting R.M. Cyclooxygenases 1 and 2. Annu. Rev. Pharmacol. Toxicol. 1998 38 1 97 120 10.1146/annurev.pharmtox.38.1.97 9597150 1998
    [Google Scholar]
  14. Funk C.D. FitzGerald G.A. COX-2 inhibitors and cardiovascular risk. J. Cardiovasc. Pharmacol. 2007 50 5 470 479 10.1097/FJC.0b013e318157f72d 18030055
    [Google Scholar]
  15. Vane J.R. Botting R.M. Mechanism of action of nonsteroidal anti-inflammatory drugs. Am. J. Med. 1998 104 3 2S 8S 10.1016/S0002‑9343(97)00203‑9 9572314
    [Google Scholar]
  16. Sharma V. Bhatia P. Alam O. Javed Naim M. Nawaz F. Ahmad Sheikh A. Jha M. Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008–2019). Bioorg. Chem. 2019 89 89 103007 10.1016/j.bioorg.2019.103007 31132600
    [Google Scholar]
  17. Zarghi A. Arfaei S. Selective COX-2 inhibitors: A review of their structure-activity relationships. Iran. J. Pharm. Res. 2011 10 4 655 683 24250402
    [Google Scholar]
  18. Chavatte P. Yous S. Marot C. Baurin N. Lesieur D. Three-dimensional quantitative structure-activity relationships of cyclo-oxygenase-2 (COX-2) inhibitors: A comparative molecular field analysis. J. Med. Chem. 2001 44 20 3223 3230 10.1021/jm0101343 11563921
    [Google Scholar]
  19. Ragab F. A. Heiba H. I. El-Gazzar M. G. Abou-Seri S. M. El-Sabbagh W. A. El-Hazek R. M. Anti-inflammatory, analgesic and COX-2 inhibitory activity of novel thiadiazoles in irradiated rats. J Photochem Photobiol B. 2017 166 285 300 10.1016/j.jphotobiol.2016.12.007
    [Google Scholar]
  20. Skrzypczak-Jankun E. Chorostowska-Wynimko J. Selman S.H. Jankun J. Lipoxygenases: A challenging problem in enzyme inhibition and drug development. Curr. Enzym. Inhib. 2007 3 2 119 132 10.2174/157340807780598350
    [Google Scholar]
  21. Iyer J.P. Srivastava P.K. Dev R. Dastidar S.G. Ray A. Prostaglandin E 2 synthase inhibition as a therapeutic target. Expert Opin. Ther. Targets 2009 13 7 849 865 10.1517/14728220903018932 19530988
    [Google Scholar]
  22. Norberg J.K. Sells E. Chang H.H. Alla S.R. Zhang S. Meuillet E.J. Targeting inflammation: Multiple innovative ways to reduce prostaglandin E₂. Pharm. Pat. Anal. 2013 2 2 265 288 10.4155/ppa.12.90 24237030
    [Google Scholar]
  23. Psarra A. Nikolaou A. Kokotou M.G. Limnios D. Kokotos G. Microsomal prostaglandin E 2 synthase-1 inhibitors: a patent review. Expert Opin. Ther. Pat. 2017 27 9 1047 1059 10.1080/13543776.2017.1344218 28627961
    [Google Scholar]
  24. Morris Z.S. Harari P.M. Interaction of radiation therapy with molecular targeted agents. J. Clin. Oncol. 2014 32 26 2886 2893 10.1200/JCO.2014.55.1366
    [Google Scholar]
  25. Provencio M. Sánchez A. Garrido P. Valcárcel F. New molecular targeted therapies integrated with radiation therapy in lung cancer. Clin. Lung Cancer 2010 11 2 91 97 10.3816/CLC.2010.n.012 20199974
    [Google Scholar]
  26. Chen D.H. Tyebally S. Malloupas M. Roylance R. Spurrell E. Raja F. Ghosh A.K. Cardiovascular disease amongst women treated for breast cancer: Traditional cytotoxic chemotherapy, targeted therapy, and radiation therapy. Curr. Cardiol. Rep. 2021 23 3 16 10.1007/s11886‑021‑01446‑x 33501515
    [Google Scholar]
  27. Meyer T. Hart I. R. Mechanisms of tumour metastasis. Eur. J. Cancer 1998 34 2 214 221 10.1016/S0959‑8049(97)10129‑0 9741324
    [Google Scholar]
  28. Manley P.W. Cowan-Jacob S.W. Buchdunger E. Fabbro D. Fendrich G. Furet P. Meyer T. Zimmermann J. Imatinib: A selective tyrosine kinase inhibitor. Eur. J. Cancer 2002 38 Suppl. 5 S19 S27 10.1016/S0959‑8049(02)80599‑8 12528769
    [Google Scholar]
  29. Lee H. Basso I.N. Kim D.D.H. Target spectrum of the BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia. Int. J. Hematol. 2021 113 5 632 641 10.1007/s12185‑021‑03126‑6 33772728
    [Google Scholar]
  30. Seke Etet P.F. Vecchio L. Nwabo Kamdje A.H. Signaling pathways in chronic myeloid leukemia and leukemic stem cell maintenance: Key role of stromal microenvironment. Cell. Signal. 2012 24 9 1883 1888 10.1016/j.cellsig.2012.05.015 22659137
    [Google Scholar]
  31. Matsui W.H. Cancer stem cell signaling pathways. Medicine (Baltimore) 2016 95 1S Suppl. 1 S8 S19 10.1097/MD.0000000000004765 27611937
    [Google Scholar]
  32. Lin Z. Zhang Q. Luo W. Angiogenesis inhibitors as therapeutic agents in cancer: Challenges and future directions. Eur. J. Pharmacol. 2016 793 793 76 81 10.1016/j.ejphar.2016.10.039 27840192
    [Google Scholar]
  33. Mourad J.J. des Guetz G. Debbabi H. Levy B.I. Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation. Ann. Oncol. 2008 19 5 927 934 10.1093/annonc/mdm550 18056916
    [Google Scholar]
  34. Jubb A.M. Harris A.L. Biomarkers to predict the clinical efficacy of bevacizumab in cancer. Lancet Oncol. 2010 11 12 1172 1183 10.1016/S1470‑2045(10)70232‑1 21126687
    [Google Scholar]
  35. Abraham J. Staffurth J. Hormonal therapy for cancer. Medicine (Abingdon) 2016 44 1 30 33 10.1016/j.mpmed.2015.10.014
    [Google Scholar]
  36. Clouthier D.L. Lien S.C. Yang S.Y.C. Colombo I. Bedard P.L. Cescon D. Spreafico A. Butler M.O. Hansen A.R. Jang R.W. Ghai S. Weinreb I. Sotov V. Gadalla R. Noamani B. Guo M. Elston S. Giesler A. Hakgor S. Jiang H. McGaha T. Brooks D.G. Haibe-Kains B. Pugh T.J. Ohashi P.S. Siu L.L. An interim report on the investigator-initiated phase 2 study of pembrolizumab immunological response evaluation (INSPIRE). J. Immunother. Cancer 2019 7 1 72 10.1186/s40425‑019‑0541‑0 30867072
    [Google Scholar]
  37. Wang D.R. Wu X.L. Sun Y.L. Therapeutic targets and biomarkers of tumor immunotherapy: Response versus non-response. Signal Transduct. Target. Ther. 2022 7 1 331 10.1038/s41392‑022‑01136‑2 36123348
    [Google Scholar]
  38. Mokhtari R.B. Homayouni T.S. Baluch N. Morgatskaya E. Kumar S. Das B. Yeger H. Combination therapy in combating cancer systematic review: Combination therapy in combating cancer background. Oncotarget 2017 8 23
    [Google Scholar]
  39. Leary M. Heerboth S. Lapinska K. Sarkar S. Sensitization of drug resistant cancer cells: A matter of combination therapy. Cancers 2018 10 12 483 10.3390/cancers10120483 30518036
    [Google Scholar]
  40. Monje M. Dietrich J. Cognitive side effects of cancer therapy demonstrate a functional role for adult neurogenesis. Behav. Brain Res. 2012 227 2 376 379 10.1016/j.bbr.2011.05.012 21621557
    [Google Scholar]
  41. Komarov P.G. Komarova E.A. Kondratov R.V. Christov-Tselkov K. Coon J.S. Chernov M.V. Gudkov A.V. A chemical inhibitor of p53 that protects mice from the side effects of cancer therapy. Science 1999 285 5434 1733 1737 10.1126/science.285.5434.1733 10481009
    [Google Scholar]
  42. Serhan C.N. The resolution of inflammation: The devil in the flask and in the details. FASEB J. 2011 25 5 1441 1448 10.1096/fj.11‑0502ufm 21532053
    [Google Scholar]
  43. Punchard N.A. Whelan C.J. Adcock I. The Journal of Inflammation. J. Inflamm. (Lond.) 2004 1 1 1 10.1186/1476‑9255‑1‑1 15813979
    [Google Scholar]
  44. Kain V. Prabhu S.D. Halade G.V. Inflammation revisited: Inflammation versus resolution of inflammation following myocardial infarction. Basic Res. Cardiol. 2014 109 6 444 10.1007/s00395‑014‑0444‑7 25248433
    [Google Scholar]
  45. Stankov S.v. Definition of inflammation, causes of inflammation and possible anti-inflammatory strategies. Open Inflamm. J. 2012 5 1 9 10.2174/1875041901205010001
    [Google Scholar]
  46. Serhan C.N. Savill J. Resolution of inflammation: The beginning programs the end. Nat. Immunol. 2005 6 12 1191 1197 10.1038/ni1276 16369558
    [Google Scholar]
  47. Blobaum A.L. Marnett L.J. Structural and functional basis of cyclooxygenase inhibition. J. Med. Chem. 2007 50 7 1425 1441 10.1021/jm0613166 17341061
    [Google Scholar]
  48. Simmons D.L. Botting R.M. Hla T. Cyclooxygenase isozymes: The biology of prostaglandin synthesis and inhibition. Pharmacol. Rev. 2004 56 3 387 437 10.1124/pr.56.3.3 15317910
    [Google Scholar]
  49. Bindu S. Mazumder S. Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: A current perspective. Biochem. Pharmacol. 2020 180 114147 10.1016/j.bcp.2020.114147 32653589
    [Google Scholar]
  50. Díaz-González F. Sánchez-Madrid F. NSAIDs: Learning new tricks from old drugs. Eur. J. Immunol. 2015 45 3 679 686 10.1002/eji.201445222 25523026
    [Google Scholar]
  51. Curry S.L. Cogar S.M. Cook J.L. Nonsteroidal antiinflammatory drugs: A review. J. Am. Anim. Hosp. Assoc. 2005 41 5 298 309 10.5326/0410298 16141181
    [Google Scholar]
  52. Ardizzone S. Bianchi Porro G. Biologic therapy for inflammatory bowel disease. Drugs 2005 65 16 2253 2286 10.2165/00003495‑200565160‑00002 16266194
    [Google Scholar]
  53. D’Haens G. Risks and benefits of biologic therapy for inflammatory bowel diseases. Gut 2007 56 5 725 732 10.1136/gut.2006.103564 17440187
    [Google Scholar]
  54. Hou J. Karin M. Sun B. Targeting cancer-promoting inflammation — have anti-inflammatory therapies come of age? Nat. Rev. Clin. Oncol. 2021 18 5 261 279 10.1038/s41571‑020‑00459‑9 33469195
    [Google Scholar]
  55. Coskun M. Vermeire S. Nielsen O.H. Novel targeted therapies for inflammatory bowel disease. Trends Pharmacol. Sci. 2017 38 2 127 142 10.1016/j.tips.2016.10.014 27916280
    [Google Scholar]
  56. Schwartz D.M. Kanno Y. Villarino A. Ward M. Gadina M. O’Shea J.J. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat. Rev. Drug Discov. 2017 16 12 843 862 10.1038/nrd.2017.201 29104284
    [Google Scholar]
  57. Jamilloux Y. El Jammal T. Vuitton L. Gerfaud-Valentin M. Kerever S. Sève P. JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun. Rev. 2019 18 11 102390 10.1016/j.autrev.2019.102390 31520803
    [Google Scholar]
  58. Altıntop M.D. Akalın Çiftçi G. Yılmaz Savaş N. Ertorun İ. Can B. Sever B. Temel H.E. Alataş Ö. Özdemir A. Discovery of small molecule COX-1 and Akt inhibitors as anti-NSCLC agents endowed with anti-inflammatory action. Int. J. Mol. Sci. 2023 24 3 2648 10.3390/ijms24032648 36768971
    [Google Scholar]
  59. Li Y. Chen J. Bolinger A.A. Chen H. Liu Z. Cong Y. Brasier A.R. Pinchuk I.V. Tian B. Zhou J. Target-based small molecule drug discovery towards novel therapeutics for inflammatory bowel diseases. Inflamm. Bowel Dis. 2021 27 Suppl. 2 S38 S62 10.1093/ibd/izab190 34791293
    [Google Scholar]
  60. Hanke T. Merk D. Steinhilber D. Geisslinger G. Schubert-Zsilavecz M. Small molecules with anti-inflammatory properties in clinical development. Pharmacol. Ther. 2016 157 163 187 10.1016/j.pharmthera.2015.11.011 26627986
    [Google Scholar]
  61. Zhang X. Xu A. Lv J. Zhang Q. Ran Y. Wei C. Wu J. Development of small molecule inhibitors targeting NLRP3 inflammasome pathway for inflammatory diseases. Eur J Med Chem. 2020 185 111822 10.1016/j.ejmech.2019.111822
    [Google Scholar]
  62. Zheng J. Fan R. Wu H. Yao H. Yan Y. Liu J. Ran L. Sun Z. Yi L. Dang L. Gan P. Zheng P. Yang T. Zhang Y. Tang T. Wang Y. Directed self-assembly of herbal small molecules into sustained release hydrogels for treating neural inflammation. Nat. Commun. 2019 10 1 1604 10.1038/s41467‑019‑09601‑3 30962431
    [Google Scholar]
  63. Han X. Sun S. Sun Y. Song Q. Zhu J. Song N. Chen M. Sun T. Xia M. Ding J. Lu M. Yao H. Hu G. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: Implications for Parkinson disease. Autophagy 2019 15 11 1860 1881 10.1080/15548627.2019.1596481 30966861
    [Google Scholar]
  64. Tavianatou A.G. Caon I. Franchi M. Piperigkou Z. Galesso D. Karamanos N.K. Hyaluronan: molecular size‐dependent signaling and biological functions in inflammation and cancer. FEBS J. 2019 286 15 2883 2908 10.1111/febs.14777 30724463
    [Google Scholar]
  65. Liu X. Xia S. Zhang Z. Wu H. Lieberman J. Channelling inflammation: Gasdermins in physiology and disease. Nat. Rev. Drug Discov. 2021 20 5 384 405 10.1038/s41573‑021‑00154‑z 33692549
    [Google Scholar]
  66. Coll R.C. Schroder K. Pelegrín P. NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol. Sci. 2022 43 8 653 668 10.1016/j.tips.2022.04.003 35513901
    [Google Scholar]
  67. Mezu-Ndubuisi O.J. Maheshwari A. The role of integrins in inflammation and angiogenesis. Pediatr. Res. 2021 89 7 1619 1626 10.1038/s41390‑020‑01177‑9 33027803
    [Google Scholar]
  68. Vineis P. Definition and classification of cancer: Monothetic or polythetic? Theor. Med. 1993 14 3 249 256 10.1007/BF00995166 8259531
    [Google Scholar]
  69. Cella D.F. Tulsky D.S. Quality of life in cancer: Definition, purpose, and method of measurement. Cancer Invest. 1993 11 3 327 336 10.3109/07357909309024860 8485655
    [Google Scholar]
  70. Hu H. Piotrowska Z. Hare P.J. Chen H. Mulvey H.E. Mayfield A. Noeen S. Kattermann K. Greenberg M. Williams A. Riley A.K. Wilson J.J. Mao Y.Q. Huang R.P. Banwait M.K. Ho J. Crowther G.S. Hariri L.P. Heist R.S. Kodack D.P. Pinello L. Shaw A.T. Mino-Kenudson M. Hata A.N. Sequist L.V. Benes C.H. Niederst M.J. Engelman J.A. Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms. Cancer Cell 2021 39 11 1531 1547.e10 10.1016/j.ccell.2021.09.003 34624218
    [Google Scholar]
  71. German J. Bloom’s syndrome. XX. The first 100 cancers. Cancer Genet. Cytogenet. 1997 93 1 100 106 10.1016/S0165‑4608(96)00336‑6 9062585
    [Google Scholar]
  72. Cowin P. Rowlands T.M. Hatsell S.J. Cadherins and catenins in breast cancer. Curr. Opin. Cell Biol. 2005 17 5 499 508 10.1016/j.ceb.2005.08.014 16107313
    [Google Scholar]
  73. Sun Y.S. Zhao Z. Yang Z.N. Xu F. Lu H.J. Zhu Z.Y. Shi W. Jiang J. Yao P.P. Zhu H.P. 2017 Risk factors and preventions of breast cancer. Int. J. Biol. Sci. 2017 13 11 1387 1397 29209143
    [Google Scholar]
  74. Minna J.D. Roth J.A. Gazdar A.F. Focus on lung cancer. Cancer Cell 2002 1 1 49 52 10.1016/S1535‑6108(02)00027‑2 12086887
    [Google Scholar]
  75. Litwin M.S. Tan H.J. The diagnosis and treatment of prostate cancer: A review. In JAMA -. JAMA 2017 317 24 2532 2542 10.1001/jama.2017.7248 28655021
    [Google Scholar]
  76. Rawla P. Epidemiology of prostate cancer. World J. Oncol. 2019 10 2 63 89 31068988
    [Google Scholar]
  77. Linares M.A. Zakaria A. Nizran P. Skin Cancer. Primary Care Clinics in Office Practice. 2015 42 4 645 659 26612377
    [Google Scholar]
  78. Gloster H.M. Jr Neal K. Skin cancer in skin of color. J. Am. Acad. Dermatol. 2006 55 5 741 760 10.1016/j.jaad.2005.08.063 17052479
    [Google Scholar]
  79. Rose-Inman H. Kuehl D. Acute Leukemia. Hematology. 2017 31 6 1011 1028 29078921
    [Google Scholar]
  80. Wyld L. Audisio R.A. Poston G.J. The evolution of cancer surgery and future perspectives. Nat. Rev. Clin. Oncol. 2015 12 2 115 124 10.1038/nrclinonc.2014.191 25384943
    [Google Scholar]
  81. Lovelace D.L. McDaniel L.R. Golden D. Long‐term effects of breast cancer surgery, treatment, and survivor care. J. Midwifery Womens Health 2019 64 6 713 724 10.1111/jmwh.13012 31322834
    [Google Scholar]
  82. Nygren P. > What is cancer chemotherapy? Acta Oncol. 2001 40 2-3 166 174 10.1080/02841860151116204 11441929
    [Google Scholar]
  83. Holford N.H. Benet L.Z. Katzung B.G. Basic and clinical pharmacology. Moscow Mc Graw Hill 1998 53 71
    [Google Scholar]
  84. Abshire D. Lang M.K. The evolution of radiation therapy in treating cancer. Semin. Oncol. Nurs. 2018 34 2 151 157 10.1016/j.soncn.2018.03.006 29606538
    [Google Scholar]
  85. Baskar R. Lee K.A. Yeo R. Yeoh K.W. Cancer and radiation therapy: Current advances and future directions. Int. J. Med. Sci. 2012 9 3 193 199 10.7150/ijms.3635 22408567
    [Google Scholar]
  86. Tsimberidou A.M. Targeted therapy in cancer. Cancer Chemother. Pharmacol. 2015 76 6 1113 1132 10.1007/s00280‑015‑2861‑1 26391154
    [Google Scholar]
  87. Padma V.V. An overview of targeted cancer therapy. Biomedicine (Taipei) 2015 5 4 19 10.7603/s40681‑015‑0019‑4 26613930
    [Google Scholar]
  88. Vanneman M. Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat. Rev. Cancer 2012 12 4 237 251 10.1038/nrc3237 22437869
    [Google Scholar]
  89. García-Aranda M. Redondo M. Immunotherapy: A challenge of breast cancer treatment. Cancers 2019 11 12 1822 10.3390/cancers11121822 31756919
    [Google Scholar]
  90. Ralhan R. Kaur J. Alkylating agents and cancer therapy. Expert Opin. Ther. Pat. 2007 17 9 1061 1075 10.1517/13543776.17.9.1061
    [Google Scholar]
  91. Kaye S.B. New antimetabolites in cancer chemotherapy and their clinical impact. Br. J. Cancer 1998 78 S3 Suppl. 3 1 7 10.1038/bjc.1998.747 9717984
    [Google Scholar]
  92. Tiwari M. Antimetabolites: Established cancer therapy. J. Cancer Res. Ther. 2012 8 4 510 519 10.4103/0973‑1482.106526 23361267
    [Google Scholar]
  93. Liang X. Wu Q. Luan S. Yin Z. He C. Yin L. Zou Y. Yuan Z. Li L. Song X. He M. Lv C. Zhang W. A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade. Eur. J. Med. Chem. 2019 171 129 168 10.1016/j.ejmech.2019.03.034 30917303
    [Google Scholar]
  94. Salmela A.L. Kallio M.J. Mitosis as an anti-cancer drug target. Chromosoma 2013 122 5 431 449 10.1007/s00412‑013‑0419‑8 23775312
    [Google Scholar]
  95. Schmidt M. Bastians H. Mitotic drug targets and the development of novel anti-mitotic anticancer drugs. Drug Resist. Updat. 2007 10 4-5 162 181 10.1016/j.drup.2007.06.003 17669681
    [Google Scholar]
  96. Henriques A.C. Ribeiro D. Pedrosa J. Sarmento B. Silva P.M.A. Bousbaa H. Mitosis inhibitors in anticancer therapy: When blocking the exit becomes a solution. Cancer Lett. 2019 440-441 64 81 10.1016/j.canlet.2018.10.005 30312726
    [Google Scholar]
  97. Pérez-Herrero E. Fernández-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur. J. Pharm. Biopharm. 2015 93 93 52 79 10.1016/j.ejpb.2015.03.018 25813885
    [Google Scholar]
  98. Mitchell M.S. Combinations of anticancer drugs and immunotherapy. Cancer Immunol. Immunother. 2003 52 11 686 692 10.1007/s00262‑003‑0427‑2 12942200
    [Google Scholar]
  99. Florea A.M. Büsselberg D. Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance and induced side effects. Cancers 2011 3 1 1351 1371 10.3390/cancers3011351 24212665
    [Google Scholar]
  100. Garcia-Oliveira P. Otero P. Pereira A.G. Chamorro F. Carpena M. Echave J. Fraga-Corral M. Simal-Gandara J. Prieto M.A. Status and challenges of plant-anticancer compounds in cancer treatment. Pharmaceuticals 2021 14 2 1 28 33673021
    [Google Scholar]
  101. Sterner R.C. Sterner R.M. CAR-T cell therapy: Current limitations and potential strategies. Blood Cancer J. 2021 11 4 69 10.1038/s41408‑021‑00459‑7 33824268
    [Google Scholar]
  102. Al-Haideri M. Tondok S.B. Safa S.H. maleki A.H. Rostami S. Jalil A.T. Al-Gazally M.E. Alsaikhan F. Rizaev J.A. Mohammad T.A.M. Tahmasebi S. CAR-T cell combination therapy: The next revolution in cancer treatment. Cancer Cell Int. 2022 22 1 365 10.1186/s12935‑022‑02778‑6 36419058
    [Google Scholar]
  103. Shah N.N. Fry T.J. Mechanisms of resistance to CAR T cell therapy. Nat. Rev. Clin. Oncol. 2019 16 6 372 385 10.1038/s41571‑019‑0184‑6 30837712
    [Google Scholar]
  104. Folkman J. Endogenous angiogenesis inhibitors. Acta Pathol. Microbiol. Scand. Suppl. 2004 112 7-8 496 507 10.1111/j.1600‑0463.2004.apm11207‑0809.x 15563312
    [Google Scholar]
  105. Keshet E. Ben-Sasson S.A. Anticancer drug targets: Approaching angiogenesis. J. Clin. Invest. 1999 104 11 1497 1501 10.1172/JCI8849
    [Google Scholar]
  106. Curtin N.J. Szabo C. Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond. Mol. Aspects Med. 2013 34 6 1217 1256 10.1016/j.mam.2013.01.006 23370117
    [Google Scholar]
  107. Curtin N. PARP inhibitors for anticancer therapy. Biochem. Soc. Trans. 2014 42 1 82 88 10.1042/BST20130187 24450632
    [Google Scholar]
  108. Guo C. Manjili M.H. Subjeck J.R. Sarkar D. Fisher P.B. Wang X.Y. Therapeutic cancer vaccines: Past, present, and future. Adv. Cancer Res. 2013 119 421 475 10.1016/B978‑0‑12‑407190‑2.00007‑1 23870514
    [Google Scholar]
  109. Melief C.J.M. van Hall T. Arens R. Ossendorp F. van der Burg S.H. Therapeutic cancer vaccines. J. Clin. Invest. 2015 125 9 3401 3412 10.1172/JCI80009
    [Google Scholar]
  110. Mei L. Zhang Z. Zhao L. Huang L. Yang X.L. Tang J. Feng S.S. Pharmaceutical nanotechnology for oral delivery of anticancer drugs. Adv. Drug Deliv. Rev. 2013 65 6 880 890 10.1016/j.addr.2012.11.005 23220325
    [Google Scholar]
  111. Sinha R. Kim G.J. Nie S. Shin D.M. Nanotechnology in cancer therapeutics: Bioconjugated nanoparticles for drug delivery. Mol. Cancer Ther. 2006 5 8 1909 1917 10.1158/1535‑7163.MCT‑06‑0141 16928810
    [Google Scholar]
  112. Siravegna G. Marsoni S. Siena S. Bardelli A. Integrating liquid biopsies into the management of cancer. Nat. Rev. Clin. Oncol. 2017 14 9 531 548 10.1038/nrclinonc.2017.14 28252003
    [Google Scholar]
  113. Pal A. Shinde R. Miralles M.S. Workman P. de Bono J. Applications of liquid biopsy in the pharmacological audit trail for anticancer drug development. Nat. Rev. Clin. Oncol. 2021 18 7 454 467 10.1038/s41571‑021‑00489‑x 33762744
    [Google Scholar]
  114. Awadasseid A. Ma X. Wu Y. Zhang W. G-quadruplex stabilization via small-molecules as a potential anti-cancer strategy. Biomed. Pharmacother. 2021 139 111550 10.1016/j.biopha.2021.111550 33831835
    [Google Scholar]
  115. Qiang H. Gu W. Huang D. Shi W. Qiu Q. Dai Y. Huang W. Qian H. Design, synthesis and biological evaluation of 4-aminopyrimidine-5-cabaldehyde oximes as dual inhibitors of c-Met and VEGFR-2. Bioorg. Med. Chem. 2016 24 16 3353 3358 10.1016/j.bmc.2016.03.061 27068889
    [Google Scholar]
  116. Liu J. Yang D. Yang X. Nie M. Wu G. Wang Z. Li W. Liu Y. Gong P. Design, synthesis and biological evaluation of novel 4-phenoxyquinoline derivatives containing 3-oxo-3,4-dihydroquinoxaline moiety as c-Met kinase inhibitors. Bioorg. Med. Chem. 2017 25 16 4475 4486 10.1016/j.bmc.2017.06.037 28716639
    [Google Scholar]
  117. Wang L.X. Liu X. Xu S. Tang Q. Duan Y. Xiao Z. Zhi J. Jiang L. Zheng P. Zhu W. Discovery of novel pyrrolo-pyridine/pyrimidine derivatives bearing pyridazinone moiety as c-Met kinase inhibitors. Eur. J. Med. Chem. 2017 141 538 551 10.1016/j.ejmech.2017.10.027 29107421
    [Google Scholar]
  118. Li J. Gu W. Bi X. Li H. Liao C. Liu C. Huang W. Qian H. Design, synthesis, and biological evaluation of thieno[2,3-d]pyrimidine derivatives as novel dual c-Met and VEGFR-2 kinase inhibitors. Bioorg. Med. Chem. 2017 25 24 6674 6679 10.1016/j.bmc.2017.11.010 29146452
    [Google Scholar]
  119. Wei D. Fan H. Zheng K. Qin X. Yang L. Yang Y. Duan Y. Zhang Q. Zeng C. Hu L. Synthesis and anti-tumor activity of [1,4] dioxino [2,3-f] quinazoline derivatives as dual inhibitors of c-Met and VEGFR-2. Bioorg. Chem. 2019 88 102916 10.1016/j.bioorg.2019.04.010 31026719
    [Google Scholar]
  120. Wang Y. Wan S. Li Z. Fu Y. Wang G. Zhang J. Wu X. Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrazolo[3,4-d]pyrimidine derivatives as BRAFV600E and VEGFR-2 dual inhibitors. Eur. J. Med. Chem. 2018 155 210 228 10.1016/j.ejmech.2018.05.054 29886324
    [Google Scholar]
  121. Oniciuc L. Amăriucăi-Mantu D. Diaconu D. Mangalagiu V. Danac R. Antoci V. Mangalagiu I.I. Benzoquinoline derivatives: An attractive approach to newly small molecules with anticancer activity. Int. J. Mol. Sci. 2023 24 9 8124 10.3390/ijms24098124 37175832
    [Google Scholar]
  122. Roskoski R. Jr Properties of FDA-approved small molecule protein kinase inhibitors. Pharmacol. Res. 2019 144 March 19 50 10.1016/j.phrs.2019.03.006 30877063
    [Google Scholar]
  123. Dai S. Zhou Z. Chen Z. Xu G. Chen Y. Fibroblast Growth Factor Receptors (FGFRs): Structures and small molecule inhibitors. Cells 2019 8 6 614 10.3390/cells8060614 31216761
    [Google Scholar]
  124. Han H. Jain A.D. Truica M.I. Izquierdo-Ferrer J. Anker J.F. Lysy B. Sagar V. Luan Y. Chalmers Z.R. Unno K. Mok H. Vatapalli R. Yoo Y.A. Rodriguez Y. Kandela I. Parker J.B. Chakravarti D. Mishra R.K. Schiltz G.E. Abdulkadir S.A. Small-molecule MYC inhibitors suppress tumor growth and enhance immunotherapy. Cancer Cell 2019 36 5 483 497.e15 10.1016/j.ccell.2019.10.001 31679823
    [Google Scholar]
  125. Du R. Huang C. Liu K. Li X. Dong Z. Targeting AURKA in cancer: Molecular mechanisms and opportunities for Cancer therapy. Mol. Cancer 2021 20 1 15 10.1186/s12943‑020‑01305‑3 33451333
    [Google Scholar]
  126. Ding Y. Chen X. Liu C. Ge W. Wang Q. Hao X. Wang M. Chen Y. Zhang Q. Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells. J. Hematol. Oncol. 2021 14 1 19 10.1186/s13045‑020‑01016‑8 33472669
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266360926250509040743
Loading
/content/journals/ctmc/10.2174/0115680266360926250509040743
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: Small Molecule ; Cellular signalling ; Cancer ; PDE4 ; COX ; Inflammation
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test