The Secret to Beating Colorectal Cancer Often Lies in Its Unique Genetic Code. Why Aren’t More Patients Being Tested for It?

Chemotherapy, radiation, and surgery are some of the most well-known treatments in health care. Their impact and limitations have been documented in countless stories of survival for decades, from Hollywood dramas to moving memoirs. For many people diagnosed with cancer, some of their first questions are about the need for and experience of these treatments.

But there’s been a quiet revolution in health care going on for years now, even while the treatments involved often remain outside the public conversation about cancer. Targeted therapies and immunotherapy, also known as precision medicine, are treatments that began to undergo rapid development after physicians gained an increased understanding of how to work with genetic material to protect against disease. These treatments use individuals’ genetics, especially the unique genetics of cancer cells, to target and dismantle cancer.

The impact of these new tools can be significant, especially in colorectal cancer. Precision medicine treatments have a greater ability to attack cancer cells while sparing healthy tissue than traditional methods such as chemotherapy. This means they may result in fewer side effects when used alone, and can provide safer long-term protection when used in conjunction with other treatments.

But targeted therapies are only effective if they can be applied, and too often, patient biomarker testing—the precursor to getting these advanced therapies—is not done. Many hospitals lack the complex protocols to automatically collect genetic material for biomarker testing, which can reveal any mutations and the nature of a person’s unique cancer. And patients don’t know to ask for it.

Many could benefit from precision medicine over traditional approaches. “It depends on the biomarker, but it’s anywhere from half to maybe about 75 percent of patients with Stage IV colon or rectal cancer get this done,” says Dr. Vanessa Wookey, a medical oncologist specializing in gastrointestinal cancers at Fox Chase Cancer Center in Philadelphia, where biomarkers are collected automatically as part of care. Those biomarkers could change the nature of how a patient is treated, particularly in late-stage gastrointestinal cancers, which are often unlikely to be cured and require advanced long-term management.

That’s why Dr. Wookey and her colleagues at Fox Chase have started an effort to get more patients tested for biomarkers so that more individuals can receive life-changing care. The best way to ensure you receive the right care at the right time is to understand the new science of precision medicine and know what questions to ask your doctor.

The Impact of Biomarkers

The great news is that precision medicine applies to a large proportion of patients–more than half of the late-stage patients with colorectal cancer Wookey sees have a mutation that affects which precision medicine treatments should be used.

“Roughly half of patients will have a KRAS mutation in the metastatic setting,” Wookey says, adding that several other mutations are also common: HER2 mutations affect about 5 percent of Stage IV patients, MSI-H mutations about 10 percent, and BRAF mutations about 10 to 15 percent.

For these patients, a targeted therapy can be transformative, either adding a new treatment approach to their care plan, or replacing a treatment that carries a greater burden or more harmful side effects. For MMR and MSI-H mutations, for example, immunotherapy can replace chemotherapy.

“Other biomarker findings such as a deficient MMR, or if the patient is MSI-High, is a good indicator that immunotherapy can be helpful. Often in those patients, we will start with immunotherapy and they will avoid chemotherapy altogether,” Wookey says. “We only need to give the patient an immunotherapy infusion every six weeks, whereas chemotherapy is usually every two or three weeks, and it’s a much longer infusion.” Immunotherapy also has fewer short-term side effects than chemotherapy, such as nausea, and can be tolerated longer without causing excessive stress on the body.

According to Dr. Namrata Vijayvergia, medical oncologist for gastrointestinal cancers at Fox Chase, the ability to treat patients using biomarkers has become an essential part of treatment. “If I did not have the availability of molecular profiling, I probably would be undertreating or incorrectly treating 50 percent of my patients,” she says. The net positive impact of adding this new approach to a physicians’ toolkit is clear.

“If you look at care as a whole, it has improved. For example, for colon cancer, the overall survival for patients has improved significantly,” Vijayvergia says, adding that the advances also benefit the quality of life. “I have patients with advanced colon cancer now on treatment for five years, and they’re still working full time. And this was something unheard of before. So tolerability and acceptability of therapy has improved for patients, which lets them have some sense of normalcy in their life, despite having a life-threatening and life-changing diagnosis.”

(Left) Namrata (Neena) Vijayvergia, MD, Associate Professor, Department of Hematology/Oncology; (Right) Vanessa B. Wookey, MD, Assistant Professor, Department of Hematology/Oncology

Breaking Down Cancer

The impact can be transformative for a patient’s care because precision medicine targets the source of cancer–flaws in cancerous cells’ genetic code that have caused them to become cancer cells.

“The reason cancer becomes cancer is that your cells develop changes or errors in the cellular code or DNA,” Wookey explains. “They cause the cells to keep growing and dividing and not listening to the body’s signals like a normal cell would.”

Only certain genes are involved in cell replication, which allows oncologists to observe patterns and identify which genes tend to drive cancer across different patients. These patterns then allow oncologists to develop precision medicine designed to dismantle the mechanisms behind cancer.

“Some specific genes, such as HER2, are what we call driver mutations,” Wookey says. “Think of it as someone putting a brick down on the gas pedal. Some of our targeted therapies are equivalent to removing that brick to try and keep that cancer from growing full speed.”

Even when there isn’t a targeted therapy to stop cancer in its tracks, these biomarkers can still help an oncologist understand how to treat it. Since certain mutations are linked to behaviors and tendencies in different cancers that oncologists have observed over time, these biomarkers can indicate whether to pursue radiation prior to, chemotherapy, or vice versa.

“BRAF, for example, tends to be a marker that indicates that cancer is more aggressive … while for patients that have deficient mismatch repair or MSI-High tumors, chemotherapy isn’t going to be as effective,” Wookey explains. “A KRAS mutation will tell us that a person’s cancer will be resistant to several medicines we use quite frequently, so when it’s present, we would avoid those.”

In the case of metastasis, biomarkers can also help physicians locate the source of the cancer after it has spread, so they can better understand its path, origin and nature.

“When we do molecular profiling, that actually guides us as to where the cancer started,” Vijayvergia says. “It’s a sort of GPS in regard to cancer.”

The impact isn’t limited to the patient. It’s important to note that, while many biomarkers fit under the umbrella of somatic mutations (meaning they are specific to the cancer and not the body as a whole), patients can also have inherited tendencies in their own genes, called germline mutations, that cause a predisposition for cancer. This type of inherited cancer risk can matter just as much for the patient’s treatment as somatic mutations–and it can also matter for the family of the patient, as they can inherit the mutation. An MMR mutation, for example, can indicate Lynch Syndrome, a condition that raises cancer risk and something that family members will then want to get tested for.

Making Sure You Benefit

Altogether, then, biomarkers not only enable precision medicine, but they can also impact traditional care, and even the preventive care of a patient’s family members. Given that biomarkers are so impactful, it’s fair to assume that they would be collected consistently as a regular part of treatment. But according to Wookey, it doesn’t happen regularly enough.

“In some studies, about 77 percent of patients got MMR testing, and about 50 percent were tested for the BRAF mutation,” Wookey says, explaining that complicated processes are part of the reason testing may not be done. “At many hospitals, a lot of testing is not done in-house, and there can be long, difficult processes that make it harder to order testing.”

Factors like insurance approval can cause delays, and when time is of the essence, as it often is with cancer, biomarker testing may get left behind.

“You don’t have the luxury to wait the three to three and a half weeks that it takes for the turnaround time for the testing to come back,” Vijayvergia says.

Particularly for patients with advanced disease, getting tested and receiving precision medicine as soon as possible is important because a patient’s ability to tolerate that treatment may decrease as time goes on. Without biomarker testing, patients may end up receiving treatment that they didn’t need, potentially negatively affecting their overall health and their ability to receive care.

“There might be patients who had a biomarker for which a targeted therapy is available, but they never got it because they weren’t tested in time for it,” Vijayvergia says. “And now they’re too weak to get treatment or to benefit from that treatment.”

That’s why Vijayvergia and Wookey have started an awareness campaign to help patients advocate for themselves–and make sure they’re getting biomarker testing done from the start when they are diagnosed with cancer. Because the solution to making sure you get biomarker testing done is actually pretty simple–first, try to go to a hospital system that provides the testing as a normal part of treatment. And second, you just need to ask–physicians, according to Vijayvergia, will often be grateful for the reminder.

“If a patient tells their doctor, ‘Can you please make sure you order that test?’, then they’re accountable to that patient,” Vijayvergia says. “The doctor is going to make sure it happens.”