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image of The Genetic and Epidemiological Dimensions of Gallbladder Cancer: Toward Effective Therapeutic Strategies

Abstract

Gallbladder Cancer (GBC) is a highly concerning malignancy, particularly prevalent in the Asian continent, attributed to irregularities in the bile tract. As of 2022, GLOBOCAN data ranks GBC as the 22nd most common cause of cancer-related mortality globally and the 6th among gastrointestinal cancers. According to recent World Cancer Research statistics, approximately 122,491 new cases of gallbladder cancer were reported by the end of 2022, ranking it 23rd among cancers in men and 20th in women worldwide. Towards the therapy of GBC, genetic studies have provided valuable insights into the molecular mechanisms driving GBC. Mutations in TP53, KRAS, ERBB2 (HER2), CDKN2A, and PIK3CA play crucial roles in tumor initiation and progression. Additionally, epigenetic modifications and aberrant signaling pathways, including Wnt/β-catenin, Notch, and PI3K/AKT/mTOR, have been implicated in GBC pathogenesis. Exploring these genetic alterations has led to targeted therapies, such as HER2 inhibitors (trastuzumab, pertuzumab) and immune checkpoint inhibitors, offering new treatment prospects. Further, current treatment approaches, including surgical resection, chemotherapy (gemcitabine-cisplatin), and radiation therapy, offer suboptimal outcomes in advanced stages of GBC. Despite its prevalence, effective therapeutic approaches and early-stage diagnostic methods remain elusive. This review provides a comprehensive overview of GBC, including its genetic mutations, epidemiology, risk factors, prevention, diagnosis, treatment options, and challenges. This work aims to offer valuable insights into the various factors directly or indirectly associated with GBC, which may assist in preparing an effective strategy against this growing malignancy.

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2025-06-24
2025-09-13

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References

  1. Cancer. Available from: https://www.who.int/health-topics/cancer#tab=tab_1
  2. Hausman D.M. What is cancer? Perspect. Biol. Med. 2019 62 4 778 784 10.1353/pbm.2019.0046 31761807
    [Google Scholar]
  3. Yin W. Wang J. Jiang L. James Kang Y. Cancer and stem cells. Exp. Biol. Med. 2021 246 16 1791 1801 10.1177/15353702211005390 33820469
    [Google Scholar]
  4. Hanahan D. Weinberg R. A. Hallmarks of cancer: The next generation. Cell 2011 144 5 646 674 10.1016/j.cell.2011.02.013 21376230
    [Google Scholar]
  5. Brugge W.R. Motor function of the gallbladder: Measurement and clinical significance. Semin. Roentgenol. 1991 26 3 226 231 10.1016/0037‑198X(91)90017‑I 1925660
    [Google Scholar]
  6. Fu S. Ding J. Liu D. Huang H. Li M. Liu Y. Tu L. Liu D. Generation of human-induced pluripotent stem cells from burn patient-derived skin fibroblasts using a non-integrative method. Int. J. Mol. Med. 2017 41 1 87 94 10.3892/ijmm.2017.3206 29115387
    [Google Scholar]
  7. Valle J.W. Kelley R.K. Nervi B. Oh D.Y. Zhu A.X. Biliary tract cancer. Lancet 2021 397 10272 428 444 10.1016/S0140‑6736(21)00153‑7 33516341
    [Google Scholar]
  8. Key Statistics for Gallbladder Cancer. 2023 Available from: https://www.cancer.org/cancer/types/gallbladder-cancer/about/key-statistics.html
  9. Sharma A. Sharma K.L. Gupta A. Yadav A. Kumar A. Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update. World J. Gastroenterol. 2017 23 22 3978 3998 10.3748/wjg.v23.i22.3978 28652652
    [Google Scholar]
  10. Global Cancer Observatory. 2025 Available from: https://gco.iarc.fr/en
  11. Roa J.C. García P. Kapoor V.K. Maithel S.K. Javle M. Koshiol J. Gallbladder cancer. Nat. Rev. Dis. Primers 2022 8 1 69 10.1038/s41572‑022‑00398‑y 36302789
    [Google Scholar]
  12. Krieghoff-Henning E. Folkerts J. Penzkofer A. Weg-Remers S. Cancer – An overview. Med. Monatsschr. Pharm. 2017 40 2 48 54 29952494
    [Google Scholar]
  13. Santucci C. Carioli G. Bertuccio P. Malvezzi M. Pastorino U. Boffetta P. Negri E. Bosetti C. La Vecchia C. Progress in cancer mortality, incidence, and survival: A global overview. Eur. J. Cancer Prev. 2020 29 5 367 381 10.1097/CEJ.0000000000000594 32740162
    [Google Scholar]
  14. Roy P.S. Saikia B.J. Cancer and cure: A critical analysis. Indian J. Cancer 2016 53 3 441 442 10.4103/0019‑509X.200658 28244479
    [Google Scholar]
  15. Roy N. Dihingia B.R. Barah P. Integrative network-based approaches identified systems-level molecular signatures associated with gallbladder cancer pathogenesis from gallstone diseases. J. Biosci. 2022 47 2 31 10.1007/s12038‑022‑00267‑6 36222131
    [Google Scholar]
  16. Dutta U. Bush N. Kalsi D. Popli P. Kapoor V.K. Epidemiology of gallbladder cancer in India. Chin. Clin. Oncol. 2019 8 4 33 10.21037/cco.2019.08.03 31484488
    [Google Scholar]
  17. Mukkamalla S.K.R. Kashyap S. Recio-Boiles A. Gallbladder Cancer. Treasure Island, FL StatPearls Publishing 2023
    [Google Scholar]
  18. Lundgren L. Muszynska C. Ros A. Persson G. Gimm O. Andersson B. Sandström P. Management of incidental gallbladder cancer in a national cohort. Br. J. Surg. 2019 106 9 1216 1227 10.1002/bjs.11205 31259388
    [Google Scholar]
  19. Schmidt M.A. Marcano-Bonilla L. Roberts L.R. Gallbladder cancer: Epidemiology and genetic risk associations. Chin. Clin. Oncol. 2019 8 4 31 10.21037/cco.2019.08.13 31484487
    [Google Scholar]
  20. Baiu I. Visser B. Gallbladder cancer. JAMA 2018 320 12 1294 10.1001/jama.2018.11815 30264121
    [Google Scholar]
  21. Kuhn E. Morbini P. Cancellieri A. Damiani S. Cavazza A. Comin C.E. Adenocarcinoma classification: Patterns and prognosis. Pathologica 2018 110 1 5 11 30259909
    [Google Scholar]
  22. Hammar S.P. Metastatic adenocarcinoma of unknown primary origin. Hum. Pathol. 1998 29 12 1393 1402 10.1016/S0046‑8177(98)90007‑7 9865824
    [Google Scholar]
  23. Song X. Hu Y. Li Y. Shao R. Liu F. Liu Y. Overview of current targeted therapy in gallbladder cancer. Signal Transduct. Target. Ther. 2020 5 1 230 10.1038/s41392‑020‑00324‑2 33028805
    [Google Scholar]
  24. Laporta M. Bárcena M. Clinical snapshot. Bronchial carcinoma, phalangeal invasion and bone resorbed with stratified squamous epithelium. Compend. Contin. Educ. Vet. 2007 29 11 691 692 18210979
    [Google Scholar]
  25. Kallini J.R. Hamed N. Khachemoune A. Squamous cell carcinoma of the skin: Epidemiology, classification, management, and novel trends. Int. J. Dermatol. 2015 54 2 130 140 10.1111/ijd.12553 25428226
    [Google Scholar]
  26. Cassarino D.S. DeRienzo D.P. Barr R.J. Cutaneous squamous cell carcinoma: A comprehensive clinicopathologic classification. J. Cutan. Pathol. 2006 33 4 261 279 10.1111/j.0303‑6987.2006.00516.x 16630176
    [Google Scholar]
  27. Li H.S. He T. Yang L.L. Adenosquamous carcinoma of the digestive system: A literature review. Scand. J. Gastroenterol. 2020 55 11 1268 1276 10.1080/00365521.2020.1832571 33070641
    [Google Scholar]
  28. Feibo L. Wei D. Lu L. Ying C. Qingsong K. Dongbo L. Primary hepatic adenosquamous carcinoma: A rare case report. Indian J. Pathol. Microbiol. 2021 64 5 Suppl. 140 10.4103/IJPM.IJPM_785_18 34135156
    [Google Scholar]
  29. Rassy E. Abou-Jaoude R. Boussios S. Assi T. Kattan J. Khaled H. Pavlidis N. Sarcoma of unknown primary: Myth or reality? J. Egypt. Natl. Canc. Inst. 2022 34 1 27 10.1186/s43046‑022‑00128‑1 35754068
    [Google Scholar]
  30. Gilbert N.F. Cannon C.P. Lin P.P. Lewis V.O. Soft-tissue Sarcoma. J. Am. Acad. Orthop. Surg. 2009 17 1 40 47 10.5435/00124635‑200901000‑00006 19136426
    [Google Scholar]
  31. Housset C. Chrétien Y. Debray D. Chignard N. Functions of the Gallbladder. Compr. Physiol. 2016 6 3 1549 1577 10.1002/cphy.c150050 27347902
    [Google Scholar]
  32. Eltawil K.M. Gustafsson B.I. Kidd M. Modlin I.M. Neuroendocrine tumors of the gallbladder: An evaluation and reassessment of management strategy. J. Clin. Gastroenterol. 2010 44 10 687 695 10.1097/MCG.0b013e3181d7a6d4 20375728
    [Google Scholar]
  33. Liao Y. Cao W.C. Li Z. Xu X. Zhang Y. Liu Z. Miao J. Zhou Y. Zhen Z. Liu D. Li H. Chai L. Wei Y. Zhang X. Zhang L. Wang J. Tian Y. Gallbladder neuroendocrine carcinoma: A report of two cases and literature review. Oncol. Lett. 2023 25 6 229 10.3892/ol.2023.13815 37153064
    [Google Scholar]
  34. Gutt C. Schläfer S. Lammert F. The treatment of Gallstone disease. Dtsch. Arztebl. Int. 2020 117 9 148 158 10.3238/arztebl.2020.0148 32234195
    [Google Scholar]
  35. Tanaja J. Lopez R.A. Meer J.M. Cholelithiasis. StatPearls Treasure Island (FL) 2022
    [Google Scholar]
  36. Pahwa R. Goyal A. Jialal I. Chronic Inflammation. StatPearls Treasure Island (FL) 2022
    [Google Scholar]
  37. Wright S.M. Aronne L.J. Causes of obesity. Abdom. Radiol. 2012 37 5 730 732 10.1007/s00261‑012‑9862‑x 22426851
    [Google Scholar]
  38. Obesity. 2022 Available from: https://www.who.int/health-topics/obesity#tab=tab_1
  39. Newland R. Blackshaw J. Waterall J. Obesity: The biggest public health challenge facing nursing this century. Br. J. Nurs. (Mark Allen Publishing), 2021 30 10 608 610 10.12968/bjon.2021.30.10.608 34037441
    [Google Scholar]
  40. Mondal K. Posa M.K. Shenoy R.P. Roychoudhury S. KRAS mutation subtypes and their association with other driver mutations in oncogenic pathways. Cells 2024 13 14 1221 10.3390/cells13141221 39056802
    [Google Scholar]
  41. Li Q. Li Z. Luo T. Shi H. Targeting the PI3K/AKT/mTOR and RAF/MEK/ERK pathways for cancer therapy. Mol. Biomed. 2022 3 1 47 10.1186/s43556‑022‑00110‑2 36539659
    [Google Scholar]
  42. Randi G. Franceschi S. La Vecchia C. Gallbladder cancer worldwide: Geographical distribution and risk factors. Int. J. Cancer 2006 118 7 1591 1602 10.1002/ijc.21683 16397865
    [Google Scholar]
  43. Dutta U. Gallbladder cancer: Can newer insights improve the outcome? J. Gastroenterol. Hepatol. 2012 27 4 642 653 10.1111/j.1440‑1746.2011.07048.x 22168580
    [Google Scholar]
  44. Rustagi T. Dasanu C.A. Risk factors for gallbladder cancer and cholangiocarcinoma: Similarities, differences and updates. J. Gastrointest. Cancer 2012 43 2 137 147 10.1007/s12029‑011‑9284‑y 21597894
    [Google Scholar]
  45. Barlow S.E. Expert committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: Summary report. Pediatrics 2007 120 Suppl. 4 S164 S192 10.1542/peds.2007‑2329C 18055651
    [Google Scholar]
  46. Rawla P. Sunkara T. Thandra K.C. Barsouk A. Epidemiology of gallbladder cancer. Clin. Exp. Hepatol. 2019 5 2 93 102 10.5114/ceh.2019.85166 31501784
    [Google Scholar]
  47. Patel P.R. De Jesus O.C.T. CT Scan. StatPearls Treasure Island (FL) 2023
    [Google Scholar]
  48. Baker H.L. Jr Campbell J.K. Houser O.W. Reese D.F. Sheedy P.F. Holman C.B. Computer assisted tomography of the head. An early evaluation. Mayo Clin. Proc. 1974 49 1 17 27 4588582
    [Google Scholar]
  49. New P.F.J. Scott W.R. Schnur J.A. Davis K.R. Taveras J.M. Computerized axial tomography with the EMI scanner. Radiology 1974 110 1 109 123 10.1148/110.1.109 4357252
    [Google Scholar]
  50. Yousaf T. Dervenoulas G. Politis M. Advances in MRI Methodology. Int. Rev. Neurobiol. 2018 141 31 76 10.1016/bs.irn.2018.08.008 30314602
    [Google Scholar]
  51. Chabanova E. Larsen L. Løgager V.B. Møller J.M. Thomsen H.S. Anvendelse af MR-skanning. Ugeskr. Laeger 2014 176 1 50 54 [Use of magnetic resonance imaging]. [Danish.]. 24629608
    [Google Scholar]
  52. Minhas A.S. Oliver R. Magnetic resonance imaging basics. Adv. Exp. Med. Biol. 2022 1380 47 82 10.1007/978‑3‑031‑03873‑0_3 36306094
    [Google Scholar]
  53. Sureshkumar A. Hansen B. Ersahin D. Role of nuclear medicine in imaging. Semin. Ultrasound CT MR 2020 41 1 10 19 10.1053/j.sult.2019.10.005 31964489
    [Google Scholar]
  54. Adams C. Banks K.P. Bone Scan. StatPearls Treasure Island (FL) 2022
    [Google Scholar]
  55. Jensen J.A. Medical ultrasound imaging. Prog. Biophys. Mol. Biol. 2007 93 1-3 153 165 10.1016/j.pbiomolbio.2006.07.025 17092547
    [Google Scholar]
  56. Ultrasound Therapy. StatPearls Treasure Island (FL) 2023
    [Google Scholar]
  57. Robertson V.J. Baker K.G. A review of therapeutic ultrasound: Effectiveness studies. Phys. Ther. 2001 81 7 1339 1350 10.1093/ptj/81.7.1339 11444997
    [Google Scholar]
  58. Pfeiffer D. Pfeiffer F. Rummeny E. Advanced X-ray imaging technology. Recent Results Cancer Res. 2020 216 3 30 10.1007/978‑3‑030‑42618‑7_1 32594383
    [Google Scholar]
  59. Luan F.J. Zhang J. Mak K.C. Liu Z.H. Wang H.Q. Low radiation X-rays: Benefiting people globally by reducing cancer risks. Int. J. Med. Sci. 2021 18 1 73 80 10.7150/ijms.48050 33390775
    [Google Scholar]
  60. Rodríguez-Fernández A. Gómez-Río M. Medina-Benítez A. Moral J.V. Ramos-Font C. Ramia-Ángel J.M. Llamas-Elvira J.M. Ferrón-Orihuela J.A. Lardelli-Claret P. Application of modern imaging methods in diagnosis of gallbladder cancer. J. Surg. Oncol. 2006 93 8 650 664 10.1002/jso.20533 16724342
    [Google Scholar]
  61. Dock Dockery G. Bakotic Bradley W. Biopsy techniques. Lower Extremity Soft Tissue & Cutaneous Plastic Surgery Saunders Ltd. 2012 127 141 10.1016/B978‑0‑7020‑3136‑6.00013‑8
    [Google Scholar]
  62. Zerbino D.D. Biopsy: Its history, current and future outlook. Lik. Sprava 1994 3-4 1 9 7975522
    [Google Scholar]
  63. Min J.K. Kwak M.S. Cha J.M. Overview of Deep Learning in gastrointestinal endoscopy. Gut Liver 2019 13 4 388 393 10.5009/gnl18384 30630221
    [Google Scholar]
  64. Saluja S. Gulati M. Garg P. Pal H. Pal S. Sahni P. Chattopadhyay T. Endoscopic or percutaneous biliary drainage for gallbladder cancer: A randomized trial and quality of life assessment. Clin. Gastroenterol. Hepatol. 2008 6 8 944 950.e3 10.1016/j.cgh.2008.03.028 18585976
    [Google Scholar]
  65. Levy I. Gralnek I.M. Complications of diagnostic colonoscopy, upper endoscopy, and enteroscopy. Best Pract. Res. Clin. Gastroenterol. 2016 30 5 705 718 10.1016/j.bpg.2016.09.005 27931631
    [Google Scholar]
  66. Hickman L. Contreras C. Gallbladder cancer. Surg. Clin. North Am. 2019 99 2 337 355 10.1016/j.suc.2018.12.008 30846038
    [Google Scholar]
  67. Neoptolemos J.P. Moore M.J. Cox T.F. Valle J.W. Palmer D.H. McDonald A.C. Carter R. Tebbutt N.C. Dervenis C. Smith D. Glimelius B. Charnley R.M. Lacaine F. Scarfe A.G. Middleton M.R. Anthoney A. Ghaneh P. Halloran C.M. Lerch M.M. Oláh A. Rawcliffe C.L. Verbeke C.S. Campbell F. Büchler M.W. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: The ESPAC-3 periampullary cancer randomized trial. JAMA 2012 308 2 147 156 10.1001/jama.2012.7352 22782416
    [Google Scholar]
  68. Feo C.F. Ginesu G.C. Fancellu A. Perra T. Ninniri C. Deiana G. Scanu A.M. Porcu A. Current management of incidental gallbladder cancer: A review. Int. J. Surg. 2022 98 106234 10.1016/j.ijsu.2022.106234 35074510
    [Google Scholar]
  69. 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]
  70. Primrose J.N. Fox R.P. Palmer D.H. Malik H.Z. Prasad R. Mirza D. Anthony A. Corrie P. Falk S. Finch-Jones M. Wasan H. Ross P. Wall L. Wadsley J. Evans J.T.R. Stocken D. Praseedom R. Ma Y.T. Davidson B. Neoptolemos J.P. Iveson T. Raftery J. Zhu S. Cunningham D. Garden O.J. Stubbs C. Valle J.W. Bridgewater J. Primrose J.N. Fox R.P. Morement H. Chan O. Rees C. Ma Y.T. Hickish T. Falk S. Finch-Jones M. Pope I. Corrie P. Crosby T. Sothi S. Sharkland K. Adamson D. Wall L. Evans J. Dent J. Hombaiah U. Iwuji C. Anthoney A. Bridgewater J. Cunningham D. Gillmore R. Ross P. Slater S. Wasan H. Waters J. Valle J.W. Palmer D. Malik H. Neoptolemos J. Faluyi O. Sumpter K. Dernedde U. Maduhusudan S. Cogill G. Archer C. Iveson T. Wadsley J. Darby S. Peterson M. Mukhtar A.A. Thorpe J.G. Bateman A. Tsang D. Cummins S. Nolan L. Beaumont E. Prasad R. Mirza D. Stocken D. Praseedom R. Davidson B. Raftery J. Zhu S. Garden J. Stubbs C. Coxon F. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): A randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019 20 5 663 673 10.1016/S1470‑2045(18)30915‑X 30922733
    [Google Scholar]
  71. Furuse J. Kasuga A. Takasu A. Kitamura H. Nagashima F. Role of chemotherapy in treatments for biliary tract cancer. J. Hepatobiliary Pancreat. Sci. 2012 19 4 337 341 10.1007/s00534‑011‑0494‑2 22456744
    [Google Scholar]
  72. Kirkwood J.M. Butterfield L.H. Tarhini A.A. Zarour H. Kalinski P. Ferrone S. Immunotherapy of cancer in 2012. CA Cancer J. Clin. 2012 62 5 309 335 10.3322/caac.20132 22576456
    [Google Scholar]
  73. Justiz Vaillant A.A. Nessel T.A. Zito P.M. Immunotherapy. StatPearls Publishing Treasure Island, FL 2023
    [Google Scholar]
  74. Karkhah A. Javanian M. Ebrahimpour S. The role of regulatory T cells in immunopathogenesis and immunotherapy of viral infections. Infect. Genet. Evol. 2018 59 32 37 10.1016/j.meegid.2018.01.015 29413883
    [Google Scholar]
  75. Verhoeven D. Stoppelenburg A.J. Meyer-Wentrup F. Boes M. Increased risk of hematologic malignancies in primary immunodeficiency disorders: Opportunities for immunotherapy. Clin. Immunol. 2018 190 22 31 10.1016/j.clim.2018.02.007 29499421
    [Google Scholar]
  76. Lamarca A. Barriuso J. McNamara M.G. Valle J.W. Molecular targeted therapies: Ready for “prime time” in biliary tract cancer. J. Hepatol. 2020 73 1 170 185 10.1016/j.jhep.2020.03.007 32171892
    [Google Scholar]
  77. Drăgănescu M. Carmocan C. Hormone therapy in breast cancer. Chirurgia 2017 112 4 413 417 10.21614/chirurgia.112.4.413 28862117
    [Google Scholar]
  78. Desai K. McManus J.M. Sharifi N. Hormonal therapy for prostate cancer. Endocr. Rev. 2021 42 3 354 373 10.1210/endrev/bnab002 33480983
    [Google Scholar]
  79. Alnasser S.M. Stem cell challenge in cancer progression, oncology and therapy. Gene 2022 840 146748 10.1016/j.gene.2022.146748 35868413
    [Google Scholar]
  80. König I.R. Fuchs O. Hansen G. von Mutius E. Kopp M.V. What is precision medicine? Eur. Respir. J. 2017 50 4 1700391 10.1183/13993003.00391‑2017 29051268
    [Google Scholar]
  81. Mahnken AH König AM Figiel JH Current technique and application of percutaneous cryotherapy. Rofo 2018 190 9 836 846 10.1055/a‑0598‑5134 29665588
    [Google Scholar]
  82. Cryosurgery R.B. Cryosurgery. Annu. Rev. Biomed. Eng. 2000 2 157 187 10.1146/annurev.bioeng.2.1.157 11701510
    [Google Scholar]
  83. Prohaska J. Jan A.H. Cryotherapy. StatPearls Publishing Treasure Island, FL 2023 Available from: https://www.ncbi.nlm.nih.gov/books/NBK482319/
    [Google Scholar]
  84. Goldberg L.H. Kaplan B. Vergilis-Kalner I. Landau J. Liquid nitrogen: Temperature control in the treatment of actinic keratosis. Dermatol. Surg. 2010 36 12 1956 1961 10.1111/j.1524‑4725.2010.01804.x 21070460
    [Google Scholar]
  85. Hoffmann N.E. Bischof J.C. Cryosurgery of normal and tumor tissue in the dorsal skin flap chamber: Part I--thermal response. J. Biomech. Eng. 2001 123 4 301 309 10.1115/1.1385838 11563754
    [Google Scholar]
  86. Farhangian M.E. Snyder A. Huang K.E. Doerfler L. Huang W.W. Feldman S.R. Cutaneous cryosurgery in the United States. J. Dermatolog. Treat. 2016 27 1 91 94 10.3109/09546634.2015.1054780 26208163
    [Google Scholar]
  87. Zimmerman E.E. Crawford P. Cutaneous cryosurgery. Am. Fam. Physician 2012 86 12 1118 1124 23316984
    [Google Scholar]
  88. Andrews M.D. Cryosurgery for common skin conditions. Am. Fam. Physician 2004 69 10 2365 2372 15168956
    [Google Scholar]
  89. Woo SM Chemotherapy for biliary tract cancer. Korean J Gastroenterol 2017 69 3 172 176 10.4166/kjg.2017.69.3.172
    [Google Scholar]
  90. Amjad M.T. Chidharla A. Kasi A. Cancer chemotherapy. StatPearls Publishing Treasure Island, FL 2023
    [Google Scholar]
  91. Williams T.M. Majithia L. Wang S.J. Thomas C.R. Jr Defining the role of adjuvant therapy: Cholangiocarcinoma and gall bladder cancer. Semin. Radiat. Oncol. 2014 24 2 94 104 10.1016/j.semradonc.2014.01.001 24635866
    [Google Scholar]
  92. Kumari N. Corless C. Warrick A. Beadling C. Nelson D. Neff T. Krishnani N. Kapoor V. Mutation profiling in gallbladder cancer in Indian population. Indian J. Pathol. Microbiol. 2014 57 1 9 12 10.4103/0377‑4929.130849 24739824
    [Google Scholar]
  93. Shukla S.K. Singh G. Shahi K.S. Bhuvan Pant P. Genetic changes of P53 and kras in gallbladder carcinoma in Kumaon region of Uttarakhand. J. Gastrointest. Cancer 2020 51 2 552 559 10.1007/s12029‑019‑00283‑0 31396884
    [Google Scholar]
  94. 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]
  95. Lee J.M. Nair J. Zimmer A. Lipkowitz S. Annunziata C.M. Merino M.J. Swisher E.M. Harrell M.I. Trepel J.B. Lee M.J. Bagheri M.H. Botesteanu D.A. Steinberg S.M. Minasian L. Ekwede I. Kohn E.C. Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: A first-in-class proof-of-concept phase 2 study. Lancet Oncol. 2018 19 2 207 215 10.1016/S1470‑2045(18)30009‑3 29361470
    [Google Scholar]
  96. Araujo L.H. Souza B.M. Leite L.R. Parma S.A.F. Lopes N.P. Malta F.S.V. Freire M.C.M. Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer. BMC Cancer 2021 21 1 193 10.1186/s12885‑021‑07884‑8 33632153
    [Google Scholar]
  97. Isermann T. Sers C. Der C.J. Papke B. KRAS inhibitors: Resistance drivers and combinatorial strategies. Trends Cancer 2025 11 2 91 116 10.1016/j.trecan.2024.11.009 39732595
    [Google Scholar]
  98. Lam K.K. Tang C.L. Tan E. Wong S.H. Cheah P.Y. KRAS mutation‐independent downregulation of MAPK/PI3K signaling in colorectal cancer. Mol. Oncol. 2022 16 5 1171 1183 10.1002/1878‑0261.13163 34919787
    [Google Scholar]
  99. Mishra R. Patel H. Alanazi S. Kilroy M.K. Garrett J.T. PI3K inhibitors in cancer: Clinical implications and adverse effects. Int. J. Mol. Sci. 2021 22 7 3464 10.3390/ijms22073464 33801659
    [Google Scholar]
  100. Peng Y. Wang Y. Zhou C. Mei W. Zeng C. PI3K/Akt/mTOR pathway and its role in cancer therapeutics: Are we making headway? Front. Oncol. 2022 12 819128 10.3389/fonc.2022.819128 35402264
    [Google Scholar]
  101. Wright S.C.E. Vasilevski N. Serra V. Rodon J. Eichhorn P.J.A. Mechanisms of resistance to PI3K inhibitors in cancer: Adaptive responses, drug tolerance and cellular plasticity. Cancers 2021 13 7 1538 10.3390/cancers13071538 33810522
    [Google Scholar]
  102. Corti F. Nichetti F. Raimondi A. Niger M. Prinzi N. Torchio M. Tamborini E. Perrone F. Pruneri G. Di Bartolomeo M. de Braud F. Pusceddu S. Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives. Cancer Treat. Rev. 2019 72 45 55 10.1016/j.ctrv.2018.11.001 30476750
    [Google Scholar]
  103. Han Y. Liu D. Li L. PD-1/PD-L1 pathway: Current researches in cancer. Am. J. Cancer Res. 2020 10 3 727 742 32266087
    [Google Scholar]
  104. Yang H. Ye D. Guan K.L. Xiong Y. IDH1 and IDH2 mutations in tumorigenesis: Mechanistic insights and clinical perspectives. Clin. Cancer Res. 2012 18 20 5562 5571 10.1158/1078‑0432.CCR‑12‑1773 23071358
    [Google Scholar]
  105. Cerchione C. Romano A. Daver N. DiNardo C. Jabbour E.J. Konopleva M. Ravandi-Kashani F. Kadia T. Martelli M.P. Isidori A. Martinelli G. Kantarjian H. IDH1/IDH2 inhibition in acute myeloid leukemia. Front. Oncol. 2021 11 639387 10.3389/fonc.2021.639387 33898313
    [Google Scholar]
  106. Chmiel P. Gęca K. Rawicz-Pruszyński K. Polkowski W.P. Skórzewska M. FGFR inhibitors in cholangiocarcinoma—A novel yet primary approach: Where do we stand now and where to head next in targeting this axis? Cells 2022 11 23 3929 10.3390/cells11233929 36497187
    [Google Scholar]
  107. Abou-Alfa G.K. Sahai V. Hollebecque A. Vaccaro G. Melisi D. Al-Rajabi R. Paulson A.S. Borad M.J. Gallinson D. Murphy A.G. Oh D.Y. Dotan E. Catenacci D.V. Van Cutsem E. Ji T. Lihou C.F. Zhen H. Féliz L. Vogel A. Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma: A multicentre, open-label, phase 2 study. Lancet Oncol. 2020 21 5 671 684 10.1016/S1470‑2045(20)30109‑1 32203698
    [Google Scholar]
  108. ten Haaft B.H.E.A. Pedregal M. Prato J. Klümpen H.J. Moreno V. Lamarca A. Revolutionizing anti-HER2 therapies for extrahepatic cholangiocarcinoma and gallbladder cancer: Current advancements and future perspectives. Eur. J. Cancer 2024 199 113564 10.1016/j.ejca.2024.113564 38266541
    [Google Scholar]
  109. Ohba A. Morizane C. Kawamoto Y. Komatsu Y. Ueno M. Kobayashi S. Ikeda M. Sasaki M. Furuse J. Okano N. Hiraoka N. Yoshida H. Kuchiba A. Sadachi R. Nakamura K. Matsui N. Nakamura Y. Okamoto W. Yoshino T. Okusaka T. Trastuzumab deruxtecan (T-DXd; DS-8201) in patients (pts) with HER2-expressing unresectable or recurrent biliary tract cancer (BTC): An investigator-initiated multicenter phase 2 study (HERB trial). J. Clin. Oncol. 2022 40 16_suppl 4006 4006 10.1200/JCO.2022.40.16_suppl.4006
    [Google Scholar]
  110. Lumish M. Chui M.H. Zhou Q. Iasonos A. Sarasohn D. Cohen S. Friedman C. Grisham R. Konner J. Kyi C. Rubinstein M. Troso-Sandoval T. Aghajanian C. Makker V. A phase 2 trial of zanidatamab in HER2-overexpressed advanced endometrial carcinoma and carcinosarcoma (ZW25-IST-2). Gynecol. Oncol. 2024 182 75 81 10.1016/j.ygyno.2023.12.028 38262242
    [Google Scholar]
  111. Ilyas F.Z. Beane J.D. Pawlik T.M. The state of immunotherapy in hepatobiliary cancers. Cells 2021 10 8 2096 10.3390/cells10082096 34440865
    [Google Scholar]
  112. Pathak A. Tomar S. Pathak S. Epigenetics and cancer: A comprehensive review. APJCB 2023 8 1 75 89 10.31557/apjcb.2023.8.1.75‑89
    [Google Scholar]
  113. Ren L. Yang Y. Li W. Yang H. Zhang Y. Ge B. Zhang S. Du G. Wang J. Recent advances in epigenetic anticancer therapeutics and future perspectives. Front. Genet. 2023 13 1085391 10.3389/fgene.2022.1085391 36685834
    [Google Scholar]
  114. Sarnik J. Popławski T. Tokarz P. BET proteins as attractive targets for cancer therapeutics. Int. J. Mol. Sci. 2021 22 20 11102 10.3390/ijms222011102 34681760
    [Google Scholar]
  115. Nara S. Esaki M. Ban D. Takamoto T. Shimada K. Ioka T. Okusaka T. Ishii H. Furuse J. Adjuvant and neoadjuvant therapy for biliary tract cancer: A review of clinical trials. Jpn. J. Clin. Oncol. 2020 50 12 1353 1363 10.1093/jjco/hyaa170 33037430
    [Google Scholar]
  116. Akhoundova Sanoyan D. McNamara M.G. Lamarca A. Valle J.W. Adjuvant chemotherapy in biliary tract cancer: State of the art and future perspectives. Curr. Opin. Oncol. 2020 32 4 364 369 10.1097/CCO.0000000000000643 32541326
    [Google Scholar]
  117. Lamarca A. Edeline J. McNamara M.G. Hubner R.A. Nagino M. Bridgewater J. Primrose J. Valle J.W. Current standards and future perspectives in adjuvant treatment for biliary tract cancers. Cancer Treat. Rev. 2020 84 101936 10.1016/j.ctrv.2019.101936 31986437
    [Google Scholar]
  118. Lamarca A. Edeline J. Goyal L. How I treat biliary tract cancer. ESMO Open 2022 7 1 100378 10.1016/j.esmoop.2021.100378 35032765
    [Google Scholar]
  119. Zhou Y. Yuan K. Yang Y. Ji Z. Zhou D. Ouyang J. Wang Z. Wang F. Liu C. Li Q. Zhang Q. Li Q. Shan X. Zhou J. Gallbladder cancer: Current and future treatment options. Front. Pharmacol. 2023 14 1183619 10.3389/fphar.2023.1183619 37251319
    [Google Scholar]
  120. Shukla H.S. Rai A. Mohapatra S.C. A review of association of dietary factors in gallbladder cancer. Indian J. Cancer 2004 41 4 147 151 10.4103/0019‑509X.13766 15659866
    [Google Scholar]
  121. Goetze T.O. Gallbladder carcinoma: Prognostic factors and therapeutic options. World J. Gastroenterol. 2015 21 43 12211 12217 10.3748/wjg.v21.i43.12211 26604631
    [Google Scholar]
  122. Saddique M.N. Saleem S. Shahid I. Javid S. Khan M.H. Iqbal J. The estrogen-gallstone connection: Uncovering the pathways. Discover Public Health 2024 21 1 113 10.1186/s12982‑024‑00232‑8
    [Google Scholar]
  123. Vineis P. Wild C.P. Global cancer patterns: Causes and prevention. Lancet 2014 383 9916 549 557 10.1016/S0140‑6736(13)62224‑2 24351322
    [Google Scholar]
  124. Stellman S.D. Resnicow K. Tobacco smoking, cancer and social class. IARC Sci. Publ. 1997 138 229 250 9353667
    [Google Scholar]
  125. McKnight-Eily LR Henley SJ Green PP Odom EC Hungerford DW Alcohol screening and brief intervention: A potential role in cancer prevention for young adults. Am J Prev Med 2017 53 3S1 S55 S62 10.1016/j.amepre.2017.04.021 28818247
    [Google Scholar]
  126. Quraishi R. Sanyal S. Dwivedi M. Moitra M. Dwivedi M. Genetic factors and microRNAs in the development of gallbladder cancer: The prospective clinical targets. Curr. Drug Targets 2024 25 6 375 387 10.2174/0113894501182288240319074330 38544392
    [Google Scholar]
/content/journals/cgt/10.2174/0115665232366089250610083533
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The Genetic and Epidemiological Dimensions of Gallbladder Cancer: Toward Effective Therapeutic Strategies
Bentham Science Publishers ; https://doi.org/10.2174/0115665232366089250610083533
/content/journals/cgt/10.2174/0115665232366089250610083533
/content/journals/cgt/10.2174/0115665232366089250610083533
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  • Article Type:     Review Article
Keywords: targeted therapies ; risk factors ; Gallbladder cancer ; early-stage diagnostic methods ; epidemiology ; gene mutation

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