Introduction: A New Era in Colon Cancer Treatment
When you hear the word cancer, your mind probably jumps to chemotherapy or radiation. But what if your own immune system could help fight the disease? Or what if drugs could zoom in like snipers, targeting only cancer cells while sparing the healthy ones? That’s exactly what immunotherapy and targeted therapy aim to do—and they’re changing the game for people with advanced colon cancer.
Advanced colon cancer, particularly stage IV, has traditionally been tough to treat. However, science is moving fast. And these newer treatments are giving hope where options used to be few. But are they for everyone? Let’s dive into how they work, who might benefit, and what the future holds.
What Is Targeted Therapy?
Imagine using a key that fits only one specific lock. That’s what targeted therapy does. Instead of killing fast-growing cells blindly (like chemo), targeted therapy homes in on specific molecules that cancer cells need to grow.
These therapies are designed to interrupt signals that tell cancer cells to grow, divide, or stay alive. They can block blood supply to tumours or directly kill cancer cells—all while leaving most healthy cells alone. Pretty neat, right?
Key Targeted Therapies Used in Colon Cancer
Here are some of the main types of targeted drugs used in colon cancer:
- Anti-EGFR therapies (like cetuximab and panitumumab): These block the epidermal growth factor receptor (EGFR), which fuels cell growth. They work best if your tumour doesn’t have RAS mutations.
- Anti-VEGF therapies (like bevacizumab): These block the formation of new blood vessels (angiogenesis) that tumours need to grow.
- BRAF inhibitors (e.g., encorafenib): Especially useful in patients whose tumours carry the BRAF V600E mutation. Often used in combination with other drugs.
- HER2-targeted therapy: Though rare in colon cancer, some tumours overexpress HER2 and may respond to drugs like trastuzumab.
Each of these therapies depends heavily on the genetic makeup of the tumour. So, molecular profiling is key.
What Is Immunotherapy?
Let’s shift gears. Immunotherapy doesn’t directly target cancer cells—instead, it wakes up your immune system. Think of it like removing the brakes from your immune cells so they can go after the tumour.
One major type is immune checkpoint inhibitors. These block proteins like PD-1 or CTLA-4, which tumours use to hide from immune attacks. Once blocked, the immune cells can “see” and attack the cancer.
MSI-H and dMMR Tumours: Why They Matter in Immunotherapy
Here’s where things get interesting. Not all colon cancers respond to immunotherapy. But those with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) do.
Why? Because these tumours have lots of mutations—basically, red flags waving at the immune system. When checkpoint inhibitors are used, the immune system finally recognises and attacks the cancer.
Testing for MSI or MMR status is now standard in advanced colon cancer because it determines whether immunotherapy could work. If your tumour is MSS (microsatellite stable) or pMMR (proficient mismatch repair), immunotherapy likely won’t help—at least, not yet.
FDA-Approved Immunotherapy Options for Advanced Colon Cancer
Let’s talk names. If your tumour is MSI-H/dMMR, you might be eligible for:
- Pembrolizumab (Keytruda): FDA-approved as a first-line treatment in MSI-H/dMMR metastatic colorectal cancer. This checkpoint inhibitor blocks PD-1.
- Nivolumab (Opdivo) and ipilimumab (Yervoy): Sometimes used together. One blocks PD-1 and the other targets CTLA-4. This duo can supercharge the immune response.
Studies show durable responses—meaning patients sometimes stay in remission for years. That’s a huge leap forward.
Who Benefits Most from These Therapies?
It’s not one-size-fits-all. These therapies shine brightest when matched to the right tumour biology. Here’s who typically benefits:
- Patients with MSI-H/dMMR tumours (for immunotherapy)
- Those with wild-type RAS (for EGFR-targeted therapy)
- Individuals with BRAF V600E mutations (for BRAF inhibitors)
- Rarely, those with HER2 amplification
In other words, testing matters. No test, no match. No match, no benefit. It’s personalised medicine in action.
Side Effects: What Patients Should Expect
These newer therapies may sound gentler than chemo—but they’re not side effect–free.
Targeted therapy side effects may include:
- Rash or dry skin
- Diarrhoea
- High blood pressure
- Liver enzyme changes
Immunotherapy side effects can be more unpredictable:
- Fatigue
- Inflammation (colitis, pneumonitis, thyroiditis)
- Autoimmune reactions
What’s different? Side effects from immunotherapy are more like the immune system going rogue. So, you’ll need a team that knows how to spot and manage these early.
Combination Therapies: Are Two Better Than One?
Sometimes, yes. For example:
- BRAF inhibitors are often given with EGFR blockers for BRAF-mutant tumours.
- Immunotherapy is being tested in combo with targeted agents or chemo—even in MSS tumours.
These combinations aim to overcome resistance or awaken a “cold” tumour (one the immune system ignores). Clinical trials are ongoing to find the best pairings.
Challenges and Limitations of These Treatments
Here’s the tough part: not everyone benefits.
- MSS tumours, which make up the majority, don’t usually respond to immunotherapy.
- Resistance can develop over time, even if the drugs work initially.
- Cost is a major concern. These therapies can be expensive, and not always fully covered.
- Side effects, though different from chemo, can still be serious.
So while these treatments are exciting, they’re not miracle cures for all.
The Future of Precision Oncology in Colon Cancer
The research train isn’t slowing down. Here’s what’s coming:
- CAR-T cell therapy: Training your own immune cells to hunt tumours. Still in early phases.
- Bispecific antibodies: These grab both immune cells and cancer cells to bring them face to face.
- Tumour vaccines: To “teach” your immune system to attack colon cancer cells.
- Artificial intelligence: To better predict who will respond to what treatment.
The ultimate goal? Turn advanced colon cancer into a chronic, manageable condition—or better yet, cure it
Conclusion: Hope on the Horizon
Immunotherapy and targeted therapy have opened new doors for people facing advanced colon cancer. While they aren’t cures for everyone, they’re rewriting the rules of what’s possible.
If you’re a patient or caregiver, ask your oncologist about testing. Because in today’s world of personalised cancer treatment, information truly is power.
References
- FDA Approves Pembrolizumab for First-Line Treatment of MSI-H Colorectal Cancer – American Cancer Society, 2020. https://www.cancer.org
- Targeted Therapy for Colorectal Cancer – National Cancer Institute, 2022. https://www.cancer.gov
- Immunotherapy for Colorectal Cancer: Where Are We Now? – Journal of Clinical Oncology, ASCO, 2021. https://ascopubs.org
- Mismatch Repair Deficiency and Microsatellite Instability in Colorectal Cancer – Mayo Clinic, 2023. https://www.mayoclinic.org
- Combination Targeted Therapy Shows Promise in BRAF-Mutant Colon Cancer – Dana-Farber Cancer Institute, 2021. https://www.dana-farber.org