A Concise Overview of Chemotherapeutic Drugs in Gastrointestinal Cancers: Mechanisms of Action and Resistance

Author(s): Shreya Sharma, Goutam Chowdhury, Anindita Chakrabarty

Gastrointestinal (GI) cancers are malignancies of the gastrointestinal tract and accessory organs of the digestive system including the esophagus, pancreas, stomach, colon, rectum, anus, liver, gallbladder, biliary system, and small intestine. These account for 28% of global cancer incidence and 35% of cancer-related mortalities. The most common type of GI cancers: colorectal and gastric cancers, rank among the top five cancers. Surgery, radiotherapy, chemotherapy, targeted therapy, and immunotherapy are available options for GI cancer treatment. With surgery being the first-line of choice, pre or post-operative chemotherapy is the second most-often used. Nevertheless, the long-term survival rate in GI cancer patients is modest due to the development of drug resistance, which can be overcome by administering various combinations of chemotherapeutic and targeted therapeutic drugs. The classic example is fluoropyrimidine, a class of cytotoxic drug used in combination with irinotecan, gemcitabine, and docetaxel to increase overall and progression-free survival in colorectal, pancreatic, and gastric cancers, respectively. Although in-depth expert reviews on select chemotherapies for the most common GI cancer types can be found, a concise overview of different drugs approved for all GI cancers is not available. In this review, we have compiled a list of the most common chemotherapeutic drugs used for GI cancers and summarized their major modes of action, intrinsic/adaptive resistance, and a few pre-clinical/clinical approaches to overcoming such resistance. We hope this manuscript will be useful for non-expert readers interested in a general overview of GI cancer chemotherapies.