Imagine you’re driving your car when suddenly, it begins to malfunction – sputtering, stalling, and generally misbehaving. What’s going on under the hood? If you’re anything like most people, you’d probably take your car to a mechanic who can identify the faulty parts and get you back on the road. In many ways, oncologists can run tests like mechanics for the human body, diagnosing and treating cancer by understanding the intricate “engine” of our cells – our DNA, both within normal cells and cancer cells. We’ll explore the world of genetic testing in oncology, focusing on three key areas: somatic mutation analysis, germline testing, and minimal residual disease detection through circulating tumor testing.
Part 1: Somatic Mutation Analysis – Finding Faulty Engine Components
When it comes to cancer, one of the main culprits is somatic mutations – genetic changes that occur in our body cells (akin to faulty engine components) and can cause cells to multiply uncontrollably, leading to tumors. Oncologists use various genetic testing methods to detect these mutations and develop targeted therapies, much like a mechanic would replace a faulty car part.
One such method is single PCR testing, which is like inspecting a specific engine component for known faults. However, this targeted approach may miss other important mutations lurking in our cellular engine. Plus, if we are interested in multiple genetic mutations, we will exhaust all the available tumor tissue leading to further biopsies and procedures to procure more tissue. Enter next-generation sequencing – a powerful diagnostic tool that checks the entire engine (our DNA) for potential faults, enabling doctors to identify both known and unexpected mutations that may be driving cancer growth. This gives oncologists a complete report of the tumor for the patient at that point in time. The goal is to find actionable mutations that can be targeted, effectively addressing the growth and spread of cancer.
Why carpet bomb with nonspecific chemotherapy when we can potentially use smart seeking bombs? Some mutations are very actionable moreso than others such as EGFR, ALK, BRAF. Some mutations tell us that certain drugs will not work at all, so no need to place patients on drugs with all potential side effect and absolutely no benefit. Or in other words, in the absence of a specific mutation, use the targeted drug in the most selective group of patients where it will work the best! See list of well known mutations at the bottom.
Circulating tumor DNA or liquid biopsies can also provide this valuable information with just the simple use of a blood draw! No need for tumor tissue or biopsies and also the added advantage of repeating the test in real time over the course of a patient’s treatment to see if new resistance mutations are occurring which may potentially be amenable to using other drugs to overcome the resistance. If the cancer is evolving quickly to resist our treatments, then our technology will need to faster identify those mutations and hopefully lead to better treatments and overall survival.
Part 2: Germline Testing – Uncovering Family Secrets in Our DNA
We inherit more than our eye color and height from our parents – sometimes, we also inherit genetic mutations that increase our risk of developing cancer. These hereditary mutations, found in our reproductive cells, are passed down from generation to generation, making germline testing an essential part of oncology.
By identifying high-risk individuals, germline testing can help families make informed decisions about cancer screening and risk-reducing measures. Plus, it can sometimes change the course of treatment for a cancer patient – because wouldn’t you want to know if your car’s engine had a hereditary flaw that could affect the state of your car and other cars in your family? If the patient is tested positive for a specific mutation, then other immediate family members can then be tested for that specific mutation. Some common hereditary mutations include those related to BRCA, Lynch Syndrome, Familial Adenomatous Polyposis (FAP), Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM), and Li-Fraumeni Syndrome. With the advent of CRISPR-Cas9 technology, we may be able to act preemptively and prevent cancer formation in these high-risk individuals.
Patients identified as high risk with a strong family history of cancers or young age for the most part will be met with a genetic counselor. After discussion of the pros, cons, risks, benefits, uncertainties, and cost of genetic testing, patients can proceed with testing being fully informed. To the patient, these results can impact their future risk for developing other cancer types and perhaps consider screening procedures that would not be considered for the general population.
In addition, doors can open for possible newew better treatments outside of traditional chemotherapies. Those with BRCA mutated breast, ovarian, pancreas cancers can potentially be treated with PARP inhibitors and consider more platinum-based chemotherapy for their tumor types. Those with Lynch syndrome or MSI-High genotypes can consider immunotherapies with a relative high rate of durable responses.
Part 3: Minimal Residual Disease and Circulating Tumor Testing – Catching Cancer on the Run
Even after successful treatment, cancer can be sneaky and leave behind a few rogue cells, known as minimal residual disease (MRD). These elusive cells can eventually cause cancer recurrence, making early detection crucial. After complete surgical resection or immunotherapies known to achieve complete remission, why wait till the house is burning down with clinical symptoms or radiographic progressive tumors if we can identify folks much earlier with identifying this matchstick of a small ember with molecular microscopic occult disease?
That’s where circulating tumor testing comes in. By analyzing a blood sample, doctors can detect traces of cancer-related DNA (ctDNA) and circulating tumor cells (CTCs) – like finding tiny engine parts that have escaped or shedded into the bloodstream. This liquid biopsy allows oncologists to monitor cancer’s response to treatment and detect possible relapses before they become a significant problem. In the not-so-distant future, instead of relying on mammograms, colonoscopies, and CT scans for breast, colon, and lung cancer screening, respectively, we may be able to screen everyone for the most common cancers using just a blood sample. We are far away from this utopian world, but the use of circulating tumor DNA becoming more mainstream makes this potentially achievable in our lifetime.
Genetic testing in oncology is a rapidly evolving field that helps doctors diagnose, treat, and monitor cancer by understanding the complex “engine” of our cells. From tracking down faulty engine components (somatic mutations) to uncovering hereditary risks (germline mutations) and capturing cancer on the run (circulating tumor testing), these cutting-edge tools are transforming the way we approach cancer care.
The next time you hear about genetic testing for cancer, remember the mechanic and the car engine – and know that the future of oncology is shifting gears to a more personalized and targeted approach. Who knows what other powerful tools we’ll discover as we continue to decode the mysteries of cancer genetics?
Example of a Foundation One Sample report. Caris, Tempus, Altera, MSKImpact, Neogenomics, Guardient are other reputable big companies than can run a comparable testing and reports. No head to head comparison or statement is being made here to say one is better than the other. Discuss with your oncologist which one they are using and perhaps why!
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. Currently practicing at the renowned Orlando Health Cancer Institute, he brings a wealth of expertise to the complex and challenging world of oncology.
Embrace the opportunity to engage with Dr. Sajeve’s expertise, and feel empowered to explore the vast expanse of oncology with renewed curiosity and understanding on “Ask MedOnCMD“