Advances in the management of gastrointestinal cancers—an upcoming role of immune checkpoint blockade

Journal of Hematology & Oncology

Weijing Sun²  Gaurav Goel¹ 

[1] Division of Medical Oncology, Department of Medicine, University of Kentucky Markey Cancer Center, Lexington 40536, KY, USA;Division of Hematology-Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, 5150 Centre Avenue, Pittsburgh 15232, PA, USA

关键词: Biomarkers;    PD-L1;    PD-1;    Nivolumab;    Pembrolizumab;    Immunotherapy;    Gastrointestinal cancers;    Checkpoint inhibitors;   

Others  :  1221326
DOI  :  10.1186/s13045-015-0185-6

 received in 2015-06-30, accepted in 2015-07-08,  发布年份 2015

【 摘 要 】

Gastrointestinal cancers are a group of highly aggressive malignancies, and novel therapeutic strategies with higher clinical efficacy are being actively sought. ‘Immunotherapy’ is now emerging as one such promising strategy for the treatment of these tumors. This article briefly reviews the recent advances that utilize targeting of immune checkpoint pathways, in the management of gastrointestinal malignancies.

【 授权许可】

   
2015 Goel and Sun.

【 参考文献 】

• [1]Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015; 65:5-29.
• [2]Shi L, Chen S, Yang L, Li Y. The role of PD-1 and PD-L1 in T-cell immune suppression in patients with hematological malignancies. J Hematol Oncol. 2013; 6:74. BioMed Central Full Text
• [3]Han EQ, Li XL, Wang CR, Li TF, Han SY. Chimeric antigen receptor-engineered T cells for cancer immunotherapy: progress and challenges. J Hematol Oncol. 2013; 6:47. BioMed Central Full Text
• [4]Li Z, Chen L, Rubinstein MP. Cancer immunotherapy: are we there yet? Exp Hematol Oncol. 2013; 2:33. BioMed Central Full Text
• [5]Ehrlich D, Wang B, Lu W, Dowling P, Yuan R. Intratumoral anti-HuD immunotoxin therapy for small cell lung cancer and neuroblastoma. J Hematol Oncol. 2014; 7:91. BioMed Central Full Text
• [6]Goel G, Sun W. Cancer immunotherapy in clinical practice–the past, present, and future. Chin J Cancer. 2014; 33:445-57.
• [7]Comprehensive molecular characterization of gastric adenocarcinoma. Nature 2014, 513:202–209.
• [8]Bang YJ, Chung HC, Shankaran V, Geva R, Catenacci DVT, Gupta S, et al. Relationship between PD-L1 expression and clinical outcomes in patients with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (MK-3475) in KEYNOTE-012. J Clin Oncol 2015, 33(suppl):abstr 4001.
• [9]Doi T, Piha-Paul SA, Jalal SI, Mai-Dang H, Yuan S, Koshiji M, et al. Pembrolizumab (MK-3475) for patients (pts) with advanced esophageal carcinoma: preliminary results from KEYNOTE-028. J Clin Oncol 2015, 33(suppl):abstr 4010.
• [10]Smyrk TC, Watson P, Kaul K, Lynch HT. Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer. 2001; 91:2417-22.
• [11]Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS et al.. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov. 2015; 5:43-51.
• [12]Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D et al.. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372:3509-20.
• [13]El-Khoueiry AB, Melero I, Crocenzi TS, Welling TH, Yau TC, Yeo W, et al. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209-040. J Clin Oncol 2015, 33(suppl):abstr LBA101.
• [14]Goel G, Sun W. Novel approaches in the management of pancreatic ductal adenocarcinoma: potential promises for the future. J Hematol Oncol. 2015; 8:44. BioMed Central Full Text
• [15]Beatty GL, Chiorean EG, Fishman MP, Saboury B, Teitelbaum UR, Sun W, Huhn RD, Song W, Li D, Sharp LL et al.. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science. 2011; 331:1612-6.
• [16]Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, Rosenberg SA. Phase 2 trial of single agent ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother. 2010; 33:828-33.
• [17]Smith AD, Roda D, Yap TA. Strategies for modern biomarker and drug development in oncology. J Hematol Oncol. 2014; 7:70. BioMed Central Full Text
• [18]Mahoney KM, Atkins MB. Prognostic and predictive markers for the new immunotherapies. Oncology (Williston Park). 2014; 28 Suppl 3:39-48.