This post is based on the interesting results published by Routy et al. Nature July 2023. I am hoping that we will soon open a protocol using FMT in cancer patients and I will announce once we’re site activated at the Orlando Health Cancer Institute.
The revolutionary world of cancer treatment is once again on the brink of a potentially transformative breakthrough, this time at the unexpected crossroads where fecal microbiota transplantation (FMT) meets immunotherapy. This novel approach, which might seem more at home in a science fiction novel than in the annals of scientific literature, suggests that the contents of our gut could unlock new levels of efficacy in cancer treatment, particularly for patients with advanced melanoma that has proven resistant to current frontline defenses.
Think of the human body as a complex ecosystem or a bustling city, with the gut microbiota representing the diverse citizenry. Just like a thriving city relies on the harmony amongst its inhabitants, our bodies depend on the intricate balance within our gut microbiota. Now, imagine if a city’s population changed – if new residents brought innovative ideas, technologies, and strategies that made the city more prosperous and resilient. That’s akin to what FMT proposes by introducing beneficial bacteria from a healthy individual’s feces into a patient’s gastrointestinal tract, potentially leading to profound systemic effects.
Recent studies have taken this concept into the realm of cancer treatment, specifically melanoma, a type of skin cancer notoriously difficult to treat in its advanced stages. Three groundbreaking clinical trials have shown not only the safety of combining FMT with anti-PD-1 immunotherapy (a treatment that unleashes the body’s immune system to attack cancer cells) but also significant promise in efficacy.
One trial recently published in Nature demonstrated a striking 65% objective response rate in previously untreated patients when FMT was paired with frontline PD-1 inhibitors, a category of drugs that includes known names like nivolumab and pembrolizumab. PD1 inhibitors as single agents typically only have a response rate of 30-40%. Another trial in patients with PD-1-refractory melanoma, whose disease had stopped responding to standard immunotherapy treatments, revealed that FMT could rekindle response to therapy, with a clinical benefit observed in 6 out of 15 patients. The third study reinforced these findings, showing clinical responses in three out of ten patients treated with FMT and reinduction of anti-PD-1 immunotherapy.
But how does this work? Let’s go back to our city analogy. Suppose a city is under siege (akin to cancer attacking the body), and its defense forces (the immune system) are struggling to fend off the invaders. Now, imagine that the new residents (beneficial bacteria introduced through FMT) bring with them unique strategies that enhance the city’s defenses, helping them outmaneuver the attackers. In scientific terms, FMT appears to reshape the gut microbiome, leading to beneficial changes in the body’s immune response and even the tumor’s immediate surroundings, the so-called tumor microenvironment.
These trials noted that responders to the treatment tended to show an increase in certain beneficial bacteria, changes in immune cell activity, and a decrease in specific immune-suppressing cells. It’s like the new residents in the city helping to coordinate better defenses and outsmarting the siege.
FMT isn’t just influencing tumor responses to therapy but also showing promise in managing immune checkpoint inhibitor (ICI)-associated colitis, a challenging side effect faced by many patients undergoing cancer immunotherapy. This breakthrough comes with the caveat that the evidence is currently based on a limited number of cases. The initial findings suggest that by altering the gut’s microbial landscape, FMT may provide rapid, significant relief for those suffering from this often debilitating condition despite multiple lines of immunosuppressive therapies.
Importantly, these studies are preliminary, and the sample sizes are relatively small. However, the implications are profound. These findings suggest a future where oncologists might not only prescribe drugs but also specific microbial cocktails tailored to boost a patient’s response to cancer therapy.
Despite the excitement, there are miles to go before FMT could become a standard part of cancer treatment. Researchers will need to confirm these findings in larger, randomized clinical trials, figure out the optimal “dose” of fecal microbiota, unravel the precise mechanisms by which these microscopic entities interact with our immune system, and establish long-term safety data.
The burgeoning field of FMT in cancer therapy represents a thrilling frontier, promising to redefine our approaches to this complex disease. As we stand on the precipice of this new era, one can’t help but marvel at the notion that the key to unlocking our body’s full cancer-fighting potential might just reside within ourselves — or more precisely, within our gut.
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“