When Cancer Outsmarted Us: A Researcher’s Quest to Stay One Step Ahead

By Lina Shoman

The Initial Victory: When Immunotherapy Works Like Magic

Immunotherapy has been a game-changer in the fight against melanoma, which is a particularly aggressive type of skin cancer often triggered by UV radiation. By utilizing the body's immune system to target cancer cells, immunotherapy has shown initial success in reducing melanoma. However, it often delivers a short-lived victory. In many cases, the cancer learns to evade the immune system, going under the radar. As Townsend, a leading researcher, explains, “When tumors evolve, many mutations don’t affect the tumor, but some help it evade immune recognition.” Understanding this process is key to pushing beyond the limits of current treatments.

When Cancer Strikes Back: Evasion and Relapse

The relapse occurs because cancer cells develop resistance mechanisms. They evolve specific mutations that make them harder for the immune system to detect. One of these mechanisms is T-cell exhaustion, a case where T-cells—the immune cells tasked with killing cancer—become “tired” over time, failing to recognize cancer as a threat. Townsend notes, “The immune system sometimes ‘backs off,’ mistaking cancer as something harmless.” Timing of immunotherapy can make a significant difference in preventing this exhaustion, as treatment needs to stimulate the immune system before it becomes desensitized. 

The Golden Hour: Timing in Cancer Treatment

A critical challenge lies in identifying the optimal moment to apply immunotherapy, known as the “golden hour” of treatment. Administering it too late could mean the immune system has already started ignoring the cancer. Townsend’s team focuses on studying specific stages of cancer mutations—primary, resistant, and metastatic—to understand when these critical changes occur. By locating the stage-specific mutations, researchers can alter treatments to each phase, giving patients a better chance of prolonged remission.

Cross-Cancer Research: Applying Tools Across Multiple Cancers

While Townsend’s team is heavily focused on melanoma, their research tools have broader applications. They are used to studying head and neck cancers, lung cancer, pancreatic cancer, leukemia, and more. Environmental factors, such as smoking, are major drivers in cancers of the head, neck, and lungs, and Townsend’s lab is analyzing genetic mutations to see which ones are most likely to speed tumor growth. He explains, “Our tools are versatile, and we’ve resisted specializing in one cancer type because our findings apply to many.”

Turning Cancer’s Strength Into Its Weakness: Breast Cancer and PARP Inhibitors

Some cancers, like breast cancer with BRCA mutations, have high mutation rates that can be turned against them. Using drugs known as PARP inhibitors, researchers push these cancers to accumulate even more mutations, ultimately causing cancer cells to “self-destruct.” In cancers with BRCA mutations, this approach has been especially promising, effectively driving cancer cells into a “death spiral,” Townsend says.

Catching It Early: New Ways to Spot Cancer Before It Spreads

Townsend’s research on stage-specific mutations is also improving early detection. Understanding which mutations occur at specific cancer stages allows for better surveillance methods, to help the chances of catching cancer before it spreads. By knowing the mutation patterns that drive early-stage growth, doctors can monitor patients more effectively, allowing for timely intervention and potentially preventing a cancer relapse or metastasis.

The Future of Cancer Treatment: Smarter, Stage-Specific Approaches

One of the greatest challenges in cancer treatment is dealing with tumor suppressor genes that lose function through mutations. Unlike oncogenes, which gain new harmful functions and can be easily targeted by drugs, tumor suppressor genes need to have their lost function restored. Despite these hurdles, Townsend remains positive and optimistic. Treatments like immunotherapy and PARP inhibitors show promise for many cancers, even the toughest metastatic cases.

With each discovery, Townsend’s team moves closer to more targeted and effective treatments. Their work in stage-specific mutation analysis and multi-cancer research provides a roadmap for future therapies that could one day make a significant difference, offering hope to patients with even the most resistant cancers.