Colorectal cancer claimed the lives of around 50,000 people in the United States in 2016. Jeopardy! champion Cindy Stowell, whose story we highlighted recently, was one of them.
March is Colorectal Cancer Awareness Month, and the need for a spotlight on this disease is as urgent as ever: CRC remains the second-leading cause of cancer-related death in the United States. Fortunately, immunotherapy could soon change that.
Immune-based treatments for colorectal cancer aren’t new. In fact, since 2003, four antibody therapies—bevacizumab, ramucirumab, cetuximab, and panitumumab—have been approved. They’ve helped, but 5-year relative survival rates remain low, just over 10%, for patients whose cancer has metastasized to other organs.
More recently, “checkpoint” immunotherapies, which have been successful in treating other metastatic cancers, were tried in colorectal cancer. Early efforts failed, until doctors noticed responses in patients with DNA repair—meaning their tumors couldn’t fix genetic “typos” and accumulated many mutations. The high level of mutations helps the immune system see the tumors as foreign and thus a target for elimination. In one clinical trial, 40% of mutation-high patients responded to the checkpoint pembrolizumab, compared to no response in patients with fewer mutations.
Another promising immunotherapy trial has combined the checkpoint atezolizumab with bevacizumab. Stephen Estrada enrolled in that combination trial and it “improved [his] life a million times over.”
Stephen’s story of success offers several lessons for addressing colorectal cancer’s impact.
First, he was diagnosed young, with stage 4 cancer before his 30th birthday. Colonoscopies are typically recommended for people over 50, but colorectal cancer rates in people under 40 have been rising for four straight decades. Getting screened sooner could allow more patients to be treated at an earlier and more manageable stage.
Second, Stephen was treated in a clinical trial. Trials offer unique access to cutting-edge treatments and care, but only about 5% of cancer patients enroll in trials. Trials like Stephen’s that combine immunotherapies will be especially important moving forward since advanced cancers regularly develop resistance to single treatments. Another such trial—funded by the Cancer Research Institute—is testing two complementary checkpoint drugs designed to unleash anti-cancer immune responses.
Third, Stephen has Lynch syndrome, a genetic condition that disrupts his cells’ DNA repair capabilities and predisposes him to colorectal cancer. This DNA repair deficiency produced tell-tale molecular signs called biomarkers that guided his doctor toward a trial that took his condition into consideration and was more likely to benefit him.
Another important biomarker that’s been established for colorectal cancer is the Immunoscore, which reflects the presence of immune cells in and around tumors, and provides great predictive power for doctors.
Not all colorectal cancers are equal, and different treatments will work better than others for different patients. Identifying and understanding biomarkers that can help predict patient response is important to selecting the right course of treatment.
Building on these initial biomarker breakthroughs, the Cancer Research Institute (CRI) partnered with Fight Colorectal Cancer to develop a blueprint aimed at advancing the way doctors approach those decisions.
CRI is also funding scientists who are working to discover new biomarkers, which could provide targets for novel and more effective immunotherapies.
CRI-funded postdoctoral fellow Hidetoshi Nakagawa, M.D., Ph.D., at the Dana-Farber Cancer Institute is uncovering how certain immune cells protect tumors, and is testing a way to convert them into anti-cancer cells. Another fellow, Dan Liu, Ph.D., at the University of California, San Francisco is determining how the production of a specific molecule found in colorectal tumors can suppress cancer-fighting activity of T cells.
Other CRI scientists are exploring the trillions of bacteria that live in our gut, which can influence tumor development and survival, for insights that could help improve prevention, detection, and treatment.
Colorectal cancer’s toll on our society is still too heavy, but with the recent advances in immunotherapy there is hope for the future. Remarkable progress has already been made, and as we learn more about the relationship between colorectal tumors and the immune system (as well as our native gut bacteria), it should reveal ample opportunities to more effectively target colorectal cancer.