본문 바로가기
KERD
논문KCI 등재

Molecular Dimensions of Gastric Cancer: Translational and Clinical Perspectives

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

주제분류병리학

초록

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

Abstract

Gastric cancer is a global health burden and has the highest incidence in East Asia. This disease is complex in nature because it arises from multiple interactions of genetic, local environmental, and host factors, resulting in biological heterogeneity. This genetic intricacy converges on molecular characteristics reflecting the pathophysiology, tumor biology, and clinical outcome. Therefore, understanding the molecular characteristics at a genomic level is pivotal to improving the clinical care of patients with gastric cancer. A recent landmark study, The Cancer Genome Atlas (TCGA) project, showed the molecular landscape of gastric cancer through a comprehensive molecular evaluation of 295 primary gastric cancers. The proposed molecular classification divided gastric cancer into four subtypes: Epstein-Barr virus–positive, microsatellite unstable, genomic stable, and chromosomal instability. This information will be taken into account in future clinical trials and will be translated into clinical therapeutic decisions. To fully realize the clinical benefit, many challenges must be overcome. Rapid growth of high-throughput biology and functional validation of molecular targets will further deepen our knowledge of molecular dimensions of this cancer, allowing for personalized precision medicine.

참고문헌 (87)

  1. Ferlay J, "Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012", Int J Cancer, 136, pp.E359~E386 (2015)
  2. 정규원, "Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2012", Cancer Research and Treatment, 47(2), pp.127~141 (2015), 대한암학회[DOI]
  3. 정규원, "Prediction of Cancer Incidence and Mortality in Korea, 2015", Cancer Research and Treatment, 47(2), pp.142~148 (2015), 대한암학회[DOI]
  4. 이경숙, "Gastric Cancer Screening in Korea: Report on the National Cancer Screening Program in 2008", Cancer Research and Treatment, 43(2), pp.83~88 (2011), 대한암학회
  5. 서민아, "Trends in Cancer Screening Rates among Korean Men and Women: Results from the Korean National Cancer Screening Survey, 2004-2012", Cancer Research and Treatment, 45(2), pp.86~94 (2013), 대한암학회
  6. Ajani JA, "Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines", Natl Compr Canc Netw, 11, pp.531~546 (2013)
  7. Waddell T, "Gastric cancer: ESMO-ESSOESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up", Ann Oncol, 24(Suppl 6), pp.57~63 (2013)
  8. Japanese Gastric Cancer Association, "Japanese gastric cancer treatment guidelines 2010 (ver. 3)", Gastric Cancer, 14, pp.113~123 (2011)
  9. Songun I, "Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial", Lancet Oncol, 11, pp.439~449 (2010)
  10. Wu CW, "Nodal dissection for patients with gastric cancer: a randomised controlled trial", Lancet Oncol, 7, pp.309~315 (2006)
  11. Bang YJ, "Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial", Lancet, 379, pp.315~321 (2012)
  12. Noh SH, "Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial", Lancet Oncol, 15, pp.1389~1396 (2014)
  13. Sakuramoto S, "Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine", N Engl J Med, 357, pp.1810~1820 (2007)
  14. Sasako M, "Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer", J Clin Oncol, 29, pp.4387~4393 (2011)
  15. Ohtsu A, "Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study", J Clin Oncol, 29, pp.3968~3976 (2011)
  16. Bang YJ, "Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial", Lancet, 376, pp.687~697 (2010)
  17. Bosman FT, "WHO classification of tumours of the digestive system" (2010), IARC Press
  18. Lauren P, "The Two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma: an attempt at a histoclinical classification", Acta Pathol Microbiol Scand, 64, pp.31~49 (1965)
  19. 최윤영, "Evolution of Gastric Cancer Treatment: From the Golden Age of Surgery to an Era of Precision Medicine", Yonsei Medical Journal, 56(5), pp.1177~1185 (2015), 연세대학교의과대학[DOI]
  20. Cancer Genome Atlas Research Network, "Comprehensive molecular characterization of gastric adenocarcinoma", Nature, 513, pp.202~209 (2014)
  21. Muro K, "A phase 1B study of pembrolizumab (Pembro; MK-3475) in patients (pts) with advanced gastric cancer", Ann Oncol, 25(Suppl 4), pp.LBA15~ (2014)
  22. Mueller A, "Selective PI3K inhibition by BKM120 and BEZ235 alone or in combination with chemotherapy in wild-type and mutated human gastrointestinal cancer cell lines", Cancer Chemother Pharmacol, 69, pp.1601~1615 (2012)
  23. Le DT, "PD-1 blockade in tumors with mismatch-repair deficiency", N Engl J Med, 372, pp.2509~2520 (2015)
  24. Huntsman DG, "Early gastric cancer in young, asymptomatic carriers of germ-line E-cadherin mutations", N Engl J Med, 344, pp.1904~1909 (2001)
  25. Lordick F, "Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial", Lancet Oncol, 14, pp.490~499 (2013)
  26. Waddell T, "Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial", Lancet Oncol, 14, pp.481~489 (2013)
  27. Satoh T, "Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN: a randomized, phase III study", J Clin Oncol, 32, pp.2039~2049 (2014)
  28. Lennerz JK, "MET amplification identifies a small and aggressive subgroup of esophagogastric adenocarcinoma with evidence of responsiveness to crizotinib", J Clin Oncol, 29, pp.4803~4810 (2011)
  29. Iveson T, "Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a doubleblind, randomised phase 2 study", Lancet Oncol, 15, pp.1007~1018 (2014)
  30. Doshi S, "Rilotumumab exposure-response relationship in patients with advanced or metastatic gastric cancer", Clin Cancer Res, 21, pp.2453~2461 (2015)
  31. "Amgen announces termination of all amgen-sponsored clinical studies of rilotumumab in advanced gastric cancer" (2014)[URL]
  32. Van Cutsem E, "Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial", J Clin Oncol, 30, pp.2119~2127 (2012)
  33. Fuchs CS, "Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial", Lancet, 383, pp.31~39 (2014)
  34. Wilke H, "Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial", Lancet Onc, 15, pp.1224~1235 (2014)
  35. Murphy G, "Meta-analysis shows that prevalence of Epstein-Barr virus-positive gastric cancer differs based on sex and anatomic location", Gastroenterology, 137, pp.824~833 (2009)
  36. Kaneda A, "Epstein-Barr virus infection as an epigenetic driver of tumorigenesis", Cancer Res, 72, pp.3445~3450 (2012)
  37. Tan P, "Genetics and molecular pathogenesis of gastric adenocarcinoma", Gastroenterology, 149, pp.1153~1162 (2015)
  38. Grogg KL, "Lymphocyte-rich gastric cancer: associations with Epstein-Barr virus, microsatellite instability, histology, and survival", Mod Pathol, 16, pp.641~651 (2003)
  39. Wang K, "Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer", Nat Genet, 43, pp.1219~1223 (2011)
  40. Bitler BG, "Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers", Med, 21, pp.231~238 (2015)
  41. An JY, "Microsatellite instability in sporadic gastric cancer: its prognostic role and guidance for 5-FU based chemotherapy after R0 resection", Int J Cancer, 131, pp.505~511 (2012)
  42. Lee HS, "Distinct clinical features and outcomes of gastric cancers with microsatellite instability", Mod Pathol, 15, pp.632~640 (2002)
  43. Choi YY, "Is microsatellite instability a prognostic marker in gastric cancer? A systematic review with meta-analysis", J Surg Oncol, 110, pp.129~135 (2014)
  44. Cristescu R, "Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes", Nat Med, 21, pp.449~456 (2015)
  45. Kim SY, "The benefit of microsatellite instability is attenuated by chemotherapy in stage II and stage III gastric cancer: results from a large cohort with subgroup analyses", Int J Cancer, 137, pp.819~825 (2015)
  46. Ribic CM, "Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer", N Engl J Med, 349, pp.247~257 (2003)
  47. Sargent DJ, "Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer", J Clin Oncol, 28, pp.3219~3226 (2010)
  48. Snyder A, "Genetic basis for clinical response to CTLA-4 blockade in melanoma", N Engl J Med, 371, pp.2189~2199 (2014)
  49. Rizvi NA, "Cancer immunology: mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer", Science, 348, pp.124~128 (2015)
  50. "Clinical Practice Guidelines in Oncology (NCCN guidelines): colon cancer, version 2.2015" (2014)[URL]
  51. Suraweera N, "Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR", Gastroenterology, 123, pp.1804~1811 (2002)
  52. Buhard O, "Multipopulation analysis of polymorphisms in five mononucleotide repeats used to determine the microsatellite instability status of human tumors", J Clin Oncol, 24, pp.241~251 (2006)
  53. Corso G, "Somatic mutations and deletions of the E-cadherin gene predict poor survival of patients with gastric cancer", J Clin Oncol, 31, pp.868~875 (2013)
  54. Wang K, "Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer", Nat Genet, 46, pp.573~582 (2014)
  55. Kakiuchi M, "Recurrent gain-of-function mutations of RHOA in diffuse-type gastric carcinoma", Nat Genet, 46, pp.583~587 (2014)
  56. Ridley AJ, "Cell migration : integrating signals from front to back", Science, 302, pp.1704~1709 (2003)
  57. Thumkeo D, "Physiological roles of Rho and Rho effectors in mammals", Eur J Cell Biol, 92, pp.303~315 (2013)
  58. Yao F, "Recurrent fusion genes in gastric cancer: CLDN18-ARHGAP26 induces loss of epithelial integrity", Cell Rep, 12, pp.272~285 (2015)
  59. Hanazono K, "Distribution of p53 mutations in esophageal and gastric carcinomas and the relationship with p53 expression", Oncol Rep, 15, pp.821~824 (2006)
  60. Lei Z, "Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil", Gastroenterology, 145, pp.554~565 (2013)
  61. Grabsch HI, "Gastric cancer pathology and underlying molecular mechanisms", Dig Surg, 30, pp.150~158 (2013)
  62. Jimeno A, "Blockade of epidermal growth factor receptor(EGFR)activity", Crit Rev Oncol Hematol, 53, pp.179~192 (2005)
  63. Terashima M, "Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II", III gastric cancer, 2012, pp.18, 5992~6000
  64. "Office of Medical Products and Tobacco" (2010)[URL]
  65. Fukuoka M, "Biomarker analyses and final overall survival results from a phase III, randomized, openlabel, first-line study of gefitinib versus carboplatin", paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS), 2011, pp.29, 2866~2874
  66. Lee J, "Towards the goal of personalized medicine in gastric cancer: time to move beyond HER2 inhibition. Part II: Targeting gene mutations and gene amplifications and the angiogenesis pathway", Discov Med, 16, pp.7~14 (2013)
  67. van Grieken NC, "KRAS and BRAF mutations are rare and related to DNA mismatch repair deficiency in gastric cancer from the East and the West: results from a large international multicentre study", Br J Cancer, 108, pp.1495~1501 (2013)
  68. Cepero V, "MET and KRAS gene amplification mediates acquired resistance to MET tyrosine kinase inhibitors", Cancer Res, 70, pp.7580~7590 (2010)
  69. Janne PA, "Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study", Lancet Oncol, 14, pp.38~47 (2013)
  70. Davies H, "Mutations of the BRAF gene in human cancer", Nature, 417, pp.949~954 (2002)
  71. Puzanov I, "Long-term outcome in BRAF(V600E) melanoma patients treated with vemurafenib: patterns of disease progression and clinical management of limited progression", Eur J Cancer, 51, pp.1435~1443 (2015)
  72. Lee SH, "BRAF and KRAS mutations in stomach cancer", Oncogene, 22, pp.6942~6945 (2003)
  73. Hurwitz H, "Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer", N Engl J Med, 350, pp.2335~2342 (2004)
  74. Sandler A, "Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer", N Engl J Med, 355, pp.2542~2550 (2006)
  75. Shah MA, "Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma", J Clin Oncol, 29, pp.868~874 (2011)
  76. Shah MA, "Gastrointestinal cancer: targeted therapies in gastric cancer-the dawn of a new era", Nat Rev Clin Oncol, 11, pp.10~11 (2014)
  77. Subramaniam D, "Cancer stem cells: a novel paradigm for cancer prevention and treatment", Mini Rev Med Chem, 10, pp.359~371 (2010)
  78. Tan DS, "Anti-cancer drug resistance: understanding the mechanisms through the use of integrative genomics and functional RNA interference", Eur J Cancer, 46, pp.2166~2177 (2010)
  79. Peinado H, "Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?", Nat Rev Cancer, 7, pp.415~428 (2007)
  80. Voutsadakis IA, "The ubiquitin-proteasome system and signal transduction pathways regulating epithelial mesenchymal transition of cancer", J Biomed Sci, 19, pp.67~ (2012)
  81. Bierie B, "Tumour microenvironment : TGFbeta : the molecular Jekyll and Hyde of cancer", Nat Rev Cancer, 6, pp.506~520 (2006)
  82. Watabe T, "Roles of TGF-beta family signaling in stem cell renewal and differentiation", Cell Res, 19, pp.103~115 (2009)
  83. Zhou J, "Activation of the PTEN", mTOR, Proc Natl Acad Sci U S A, pp.2007, 104[DOI]
  84. Hirsch HA, "Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission", Cancer Res, 69, pp.7507~7511 (2009)
  85. Choong-kun Lee, "Cumulative Metformin Use and Its Impact on Survival in Gastric Cancer Patients After Gastrectomy", Annals of Surgery, 263(1), pp.96~102 (2016), Ovid Technologies (Wolters Kluwer Health)[DOI]
  86. Takaishi S, "Identification of gastric cancer stem cells using the cell surface marker CD44", Stem Cells, 27, pp.1006~1020 (2009)
  87. Wadhwa R, "Gastric cancermolecular and clinical dimensions", Nat Rev Clin Oncol, 10, pp.643~655 (2013)

관련 논문AI추천

이 간행물의 다른 논문 (11건)