Immunotherapy for Colorectal Cancer
How is Immunotherapy for Colorectal Cancer Changing the Outlook for Patients?
Reviewed by
Luis A. Diaz Jr., MD
Memorial Sloan Kettering Cancer Center
Immunotherapy for colorectal cancer can be effective, especially in cases where tumors show high microsatellite instability.
Colorectal cancer, referring to both colon cancer and rectal cancer, begins in the lining of the colon or rectum and has the ability to spread to other organ systems and lymph nodes. Over 95% of colorectal cancers are adenocarcinomas, a type of tumor that originates in the mucus-producing glands of the colon or rectum. Recently, the role of Lynch syndrome—an inheritable genetic disorder—in the development of colorectal has come to be recognized. It’s estimated that Lynch syndrome results in about 5,000 new cases of colorectal cancer year in the United States.
Colorectal cancer is the third most common cancer type in the U.S. and the second most deadly. Globally, there are approximately 1.8 million cases of colorectal cancer diagnosed each year, along with over 900,000 deaths caused by the disease. In 2023, there will be an estimated 150,000 new cases of colorectal cancer diagnosed and 53,000 colorectal cancer-related deaths in the United States alone.
Though overall death and incidence rates among both men and women have declined over the past two decades—largely due to screening tests that detect pre- and early stage disease—underuse of these screening tests means that only 40% of colorectal cancers are diagnosed as early stage, when the survival rate is highly favorable at 90%. As such, new treatments for colorectal cancer are urgently needed.
Colorectal Cancer Treatment Options
Traditional treatments for colorectal cancer include chemotherapy, radiation, and surgery. Immunotherapy is class of treatments that take advantage of a person’s own immune system to help kill cancer cells. There are several FDA-approved immunotherapy options for colorectal cancer, including for tumors with high microsatellite instability (MSI-H) or DNA mismatch repair deficiency (dMMR).
- Bevacizumab (Avastin®): a monoclonal antibody that targets the VEGF/VEGFR pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced colorectal cancer, including as a first-line therapy
- Cetuximab (Erbitux®): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced, EGFR-positive colorectal cancer, including as a first-line therapy
- Panitumumab (Vectibix®): a monoclonal antibody that targets the EGFR pathway; approved for subsets of patients with advanced, EGFR-positive colorectal cancer
- Ramucirumab (Cyramza®): a monoclonal antibody that targets the VEGF/VEGFR2 pathway and inhibits tumor blood vessel growth; approved for subsets of patients with advanced colorectal cancer, including as a first-line therapy
Checkpoint Inhibitors
- Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced colorectal cancer that has DNA mismatch repair deficiency (dMMR)
- Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved in combination with nivolumab for subsets of patients with advanced, colorectal cancer that has high microsatellite instability (MSI-H)
- Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced colorectal cancer that has high microsatellite instability (MSI-H), including in combination with ipilimumab
- Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with advanced colorectal cancer that has high microsatellite instability (MSI-H), DNA mismatch repair deficiency (dMMR), or high tumor mutational burden (TMB-H), including as a first-line treatment
Many immunotherapies that show promise in addressing other types of cancer are in clinical testing for colorectal cancer.
CRI’s Impact on Colorectal Cancer
The Cancer Research Institute has a long history of supporting scientific research for the advancement of colorectal cancer treatment, seeing many major breakthroughs that have made immunotherapy a promising approach for this disease.
- One landmark study in 1998 by Haruo Ohtani, M.D., provided early evidence that immunotherapy treatments can act as a catalyst or enhancement for ideal immunologic conditions that could extend the lives of colorectal cancer patients.
- The recent development of the Immunoscore tool, by Jérôme Galon, Ph.D., a new way to classify tumors, better predicts the rate of relapse and survival in patients with colorectal cancers, providing essential prognostic information that can then improve the confidence of clinical decisions and rational stratification of patient treatment.
- Research by Dirk Jäger, M.D., a member of the CRI clinical trials network at the University of Heidelberg in Germany, elucidated how immune parameters correlate with prognosis in colorectal cancer.
- In one study, former CRI postdoctoral fellow Eran Elinav, M.D., Ph.D., along with former CRI predoctoral scholar Till Strowig, Ph.D., showed that deficiencies in caspase-1, an enzyme involved in the activation and maturation of inflammatory immune molecules, resulted in enhanced tumor formation in a colitis-associated colorectal cancer model.
- The CRI Clinical Accelerator is currently sponsoring an immunotherapy trial (NCT02963831) that is studying the combination of a PD-L1 checkpoint inhibitor and an oncolytic virus in patients with advanced colorectal cancer, led by Kunle Odunsi, M.D., Ph.D., of Roswell Park Comprehensive Cancer Center, and Dmitriy Zamarin, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center.
Explore CRI’s current funding for colorectal cancer research in our funding directory.
Colorectal Cancer Clinical Trial Targets
Discover the different proteins, pathways, and platforms that scientists and physicians are pursuing to develop new cancer treatments. Use this information to consider your clinical trial options.
Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers (known as antigens) on cancer cells, in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in colorectal cancer clinical trials include:
- Angiopoietin: this pathway can promote the growth of blood vessels in tumors
- DLL/Notch: a pathway that can promote cell growth
- EGFR: a pathway that controls cell growth and is often mutated in cancer
- HER2: a pathway that controls cell growth and is commonly overexpressed in cancer and associated with metastasis
- TROP2: a protein that is commonly overexpressed in cancer and appears to aid cancer cell self-renewal, proliferation, invasion, and survival
- VEGF/VEGF-R: a pathway that can promote blood vessel formation in tumors
Find an immunotherapy clinical trial
Create a profile and fill out a questionnaire to identify immunotherapy clinical trials for which you may be eligible.
Need more information? Learn more about clinical trials.
