Fighting Colorectal Cancer with Immunotherapy: What You Need to Know

While colorectal cancer (CRC) is the third most diagnosed cancer and the third leading cause of cancer deaths in American women and men, thanks to early screening and advanced treatment, the death rates due to CRC have dropped by half in the past three decades [1]. Today, nine out of 10 patients live beyond the five year mark from diagnosis, if their disease is caught in it’s early stages.

This means CRC is no longer a death sentence. Like many cancers, the treatment of CRC involves surgery to remove the cancerous tissue and depending on the stage and severity of disease, a follow-up treatment of chemotherapy or radiotherapy agents is required to restrict the growth of any remaining tumor cells. Recent advances in technology and treatment options have made more options available for patients, be it advanced screening options, or revolutionary therapies like immunotherapy.

Treatment Options: What Patients Need to Know?

Each cancer diagnosis is different, and a patient’s treatment depends on the stage and severity of the disease. CRC, like many other cancers, is divided into five well-defined stages (Stage 0 to 4). This framework helps doctors and clinicians to provide the best possible care for the patients[2].

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A Stage by Stage Guide

Stage 0

• When cancer cells are present but only in the inner lining of the colon or rectum.
• Surgery can remove the tumor and is the only treatment needed.

Stage 1:

• When cancer grows in deeper layers of the colon or rectum wall but hasn’t grown beyond it.
• Surgery can remove the cancer tissue and if any high-grade tumors are present nearby, healthy tissue is also removed. 

Stage 2

• Cancer has grown through the wall of intestine and started spreading to nearby tissue but not lymph nodes.
• For such cancers surgery is standard, often preceded by by a neoadjuvant therapy such as chemotherapy or immunotherapy, if the tumor is aggressive.

Stage 3:

• Cancer has spread to nearby organs and lymph nodes.
• Surgery followed by adjuvant chemotherapy is used to eliminate remaining cancer cells.
• Radiation may be used if cancer has spread to nearby organs or if surgery isn’t an option.

Stage 4

• Cancer has metastasized to various organs, often to liver, lungs, brain, or peritoneal cavity.

Treatment options are limited for such patients and doctors primarily treat these tumors with systemic chemotherapy. They administer chemotherapy before surgery to shrink tumors and follow it with surgery if feasible.

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New Colorectal Cancer Treatments: How Precision Medicine Is Changing Care

New targeted therapies and immunotherapies are revolutionizing CRC treatment. Advances in research have deepened our understanding of CRC, revealing crucial proteins, signaling molecules, and pathways that drive cancer growth and spread. This knowledge has led to the development of more precise drugs that target these specific mechanisms, enhancing treatment effectiveness.

Unlike traditional chemotherapy, which attacks all fast-dividing cells, targeted therapies focus on specific molecules or pathways that help the CRC grow. For example, drugs like Bevacizumab and Ramucirumab work by hindering new blood vessel formation, which is crucial for tumor growth.

While other drugs, like Cetuximab, target special protein receptors to halt tumor cell division and growth. These treatments can be used alone, in combination with chemotherapy, or with other targeted drugs.

Newer therapies, like Regorafenib, block multiple signaling pathways that tumors use for survival. Targeted therapy drugs, like Encorafenib, can target specific mutations and attack the abnormal BRAF proteins found in CRC cells. These advancements mark significant progress in tailoring treatments to individual cancer profiles, offering hope for more effective outcomes in CRC management.

Immunotherapy is revolutionizing CRC treatment by leveraging the body’s own defense system to fight cancer. Unlike traditional treatments, immunotherapy can offer more targeted, durable responses with fewer side effects.  Continued efforts in the field of immunotherapy now are bearing fruit for patients and certain types of CRC are completely treatable with immunotherapy.

Immune Checkpoint Inhibitors for Colorectal Cancer: A Breakthrough Treatment

One of the most effective immunotherapies for CRC are immune checkpoint inhibitors (ICIs). These drugs “release the brakes” on immune cells, enabling them to attack cancer. ICIs are particularly successful in tumors with mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H)—genetic features that cause an accumulation of mutations, making tumors more visible to the immune system. These type of CRC tumors account for about 15-18% of stage II CRCs, 9-10% of stage III, and 4-5% of stage IV cases [3].

When to Use Immunotherapy for Colon Cancer?

Immunotherapy can treat some types of CRCs safely and effectively. ICIs like Keytruda (pembrolizumab), are now FDA-approved as a first-line treatment for metastatic CRC that are MSI-H/dMMR.  Along with CRC, PD-1 inhibitor, Keytruda now has 40 FDA approvals for treating 18 different cancer types.

CAR-T Cell Therapy for Colorectal Cancer: A Promising Frontier

Another groundbreaking approach is Chimeric Antigen Receptor T-cell (CAR-T) therapy, which involves engineering a patient’s T cells to specifically target cancer cells. While currently approved for blood cancers like leukemia and lymphoma, clinical trials are showing promise for CRC. A novel CAR-T therapy, GCC19CART, recently demonstrated an 80% response rate in a small group of patients with refractory metastatic CRC. As research advances, CAR-T may provide new hope for CRC patients who do not respond to other treatments.

The Future of CRC Treatment

CRC treatment has come a long way, offering more options than ever before. While surgery, chemotherapy, and radiation are still important, newer treatments like targeted therapy and immunotherapy are making a big difference. Immune checkpoint inhibitors and CAR-T cell therapy are giving hope to patients, especially those with advanced or hard-to-treat CRC. At the same time, early detection and a healthy lifestyle remain the best ways to prevent CRC. With continued research and medical advancements, the future of CRC treatment looks brighter, bringing new hope to patients and their families.

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[1] Colorectal Cancer — Cancer Stat Facts

[2] Diagnosis and Staging – NCI

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