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Cancer is unique among human diseases in the way it manifests a betrayal of our bodies, multiplying our cells out of control, while stealing our health, vitality, and lives in the process. Throughout the history of modern medicine, we have tried countless avenues of research, detection, and therapies in the battle to treat and cure cancer in its myriad forms. Some of those detection methods involve things as seemingly unusual as training dogs to sniff them out and find them early, as portrayed in the film A Dog’s Journey, while treatments include surgeries, radiation, and chemotherapy.
Hoping for a magic bullet, something which will cure all cancers all of time, usually hinges on a misunderstanding of what cancer is, treating it as a monolith instead of a suite of different diseases. In reality, research into new therapies typically hopes for something which can help a subset of patients most of the time. Now, we might have another tool in our arsenal. One which, at least in its first trial, has shown to be shockingly effective, entirely eliminating cancer in every one of the trial participants.
Researchers at Memorial Sloan Kettering Cancer Center recently published the results of a trial which armed patients’ own immune systems to fight against a specific type of rectal cancer. In the trial, which had a small population of only 14 patients to start with, immunotherapy treatment was effective at shrinking and eliminating rectal cancer. By the time the trial was done, not a single patient had even a trace of the cancer remaining in their bodies. The results of the trial were published in The New England Journal of Medicine.
In conventional cancer scenarios, patients often undergo targeted radiation or chemotherapy in an effort to reduce the size of their tumors until they can be surgically removed with minimal collateral damage. In the case of rectal cancers, however, those therapies often have undesired consequences. Because of the location of the cancer, patients often undertake irreversible damage to their bladder, digestive system, and reproductive organs, resulting in incontinence and infertility, not to mention an immeasurable psychological and emotional impact. These therapies can be life saving but come at a cost.
Doctors at MSK set out to see if immunotherapy could take the place of radiation or chemotherapy in shrinking the tumors while avoiding some of the nastier side effects. For the trial, they sought patients with a specific type of rectal cancer caused by a deficiency in mismatch repair. These cancers, known as MMRd, account for between 5% and 10% of all rectal cancer patients and also occur in other types of cancer. Prior studies have shown that MMRd tumors are particularly susceptible to immunotherapies, even once they’ve metastasized to other parts of the body. In this case, all of the study participants were either stage 2 or 3, but their cancers had not yet metastasized.
Because the tumors are caused by a deficiency in mismatch repair, they stack up mutations like a dragon hoarding gold. Those mutations would normally trigger an immune response, killing the cells before they become dangerous, but tumors take advantage of a failsafe built into our immune system.
Immune cells have a safeguard check which they use to prevent themselves from attacking normal cells. Cancer cells shouldn’t set off the immune system’s safety alarm, but they do. It’s almost as if they send out an alert telling your immune system there’s nothing to see here, giving them free rein to grow unchecked. It’s like your immune system is blindfolded and the cancer is running free, ransacking the house while your built-in security system is none the wiser.
Immunotherapy effectively removes the blindfold by inhibiting the checkpoint, putting your immune cells back on alert. Once they’re on the lookout, the cancer cells stick out like a neon sign and your immune system gets to work.
Each patient was given an injection of Jemperli — an immune checkpoint inhibitor — once every three weeks for six months. According to a press release, patients noticed a significant improvement in symptoms after only one treatment. One by one, as they continued to return for treatments and monitoring, researchers realized their tumors were shrinking and, ultimately, disappearing. By the end of the trial, all 14 were entirely in remission and needed no radiation, chemotherapy, or surgery of any kind.
Today, approximately two years have passed since the trial began and there are no signs that the cancer has returned in any of the study patients. MSK is continuing their work and encouraging rectal cancer patients to get tested to see if their tumor might have the MMRd mutation. They are also expanding the research to look at the potential efficacy of the treatment in cancers of other types and locations.
As with all avenues of research, scientists need more time, study, and observation to validate their initial findings. However, if the results hold steady, immunotherapy might be a breakthrough treatment for MMRd cancers.