Molecular Signatures Are Redefining Cancer Treatment

New studies demonstrate that treating cancer based on its molecular vulnerabilities, rather than where it originated, could translate to better outcomes for patients

The way oncologists treat cancer is undergoing a tectonic shift. For decades, doctors have focused on where cancer originated: breast cancer, lung cancer, pancreatic cancer. So distinct have these cancers seemed that oncologists often specialize in just one type.

But thanks to rapid scientific advances, particularly in genomics, the way we define and approach cancer is changing significantly. Countless studies have shown that each cancer’s molecular profile provides more clinically actionable intel than its site of origin.

As normal human cells slowly acquire mutations that turn them into cancer cells, they pull from the same bag of biological tricks to evade detection by the immune system, grow quickly, and slurp up different sources of energy to outcompete other cells. Sometimes the trick involves turning off a gene that’s designed to prevent the occurrence of cancer; sometimes it’s turning on genes that boost its cancerous traits. Because those tricks aren’t specific to a site of origin, it could be that one patient’s colon cancer and another patient’s breast cancer are actually more biologically similar than two patients’ breast cancers.

New tests allow pathologists and oncologists to generate a molecular profile for each cancer. This is a genomic hit list, aimed at revealing the biological mechanisms fueling the cancer — and, with luck, identifying associated molecular vulnerabilities that can be exploited to kill the cancer.

That hit list wouldn’t be terribly useful without treatments tailored to those vulnerabilities. So-called targeted therapies, which typically work only for cancers driven by a certain genetic signature, have answered that need. They emerged in the late 1990s and early 2000s, but more recently development of these therapies has exploded, matching the pace of scientific discoveries of new molecular targets in a broader range of cancers. Today, the FDA has approved several targeted therapies based on molecular profile rather than the cancer’s original location. These therapies are typically approved together with a companion diagnostic test to determine which patients’ cancers have the matching profile.

At the recent annual meeting of the American Society of Clinical Oncology — one of the biggest cancer research gatherings of the year — newly reported results showed that the ability to target therapies for better patient outcomes continues to gain traction.

In one study, researchers identified a new subset of breast cancers, defined as tumors with low levels of the HER2 protein. This new class represents a significant fraction of new breast cancer cases each year. The study wasn’t terribly large — with 557 patients on three continents — but patients with cancer matching this new classification had significantly improved outcomes after receiving a treatment that targets the HER2 protein.

For cancer patients, it’s just as important to identify the right therapy as it is to rule out unnecessary ones. A separate study focused on 500 patients aged 55 and older who had a particular type of low-grade breast cancer. Researchers found that patients whose tumors had low levels of a certain protein biomarker, known as Ki67, could safely avoid radiation therapy without any change in their health outcomes after five years.

Finally, one study generated truly stunning results — but it was an extremely small trial of just 12 patients, so larger follow-up studies will be important to see if these results were a fluke. All patients had stage 2 or stage 3 rectal cancer with a very specific molecular profile. The researchers’ plan was simple: treat these patients for six months with a targeted therapy, and then have them undergo chemotherapy, radiation, and surgery. But after six months of treatment, no cancer could be found in any of the 12 patients. Six months later, the patients remained cancer-free, with no need for any additional therapy.

With these and many other advances, it’s clear that molecular characterization of cancer should now be considered essential for optimal patient care. Scientists and physicians continue to hone these classifications of cancer, but patients around the world are already seeing the benefit of this new approach.

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