Fighting Rare Cancers With The Immune System

erkel cell carcinoma (MCC) begins as a painless lump on the skin that can seem completely harmless but if left untreated the cancer can spread rapidly and be fatal.

“It will initially seem completely innocuous,” says Dr. Marcus Butler, oncologist at the Princess Margaret Cancer Centre in Toronto. “The patient may notice a lump and think it’s something that will go away but it continues to grow and can grow quite rapidly over the course of several weeks.”
MCC most often occurs in people over the age of 50. Prolonged sun exposure and a weakened immune system are both risk factors which can increase a person’s chance of developing MCC.

If the cancer is caught in time it can be removed by surgical resection, but MCC can metastasize rapidly to other parts of the body. In the event of metastasis, surgical resection may no longer be an option.

The gruelling effects of traditional treatments

Radiation therapy and chemotherapy are also used to treat MCC, but both have their drawbacks. Chemotherapy is a gruelling process for anyone, but as the majority of those diagnosed with MCC will be advanced in years, chemotherapy can be particularly debilitating. Although most patients who undergo chemotherapy will see a shrinkage in tumour size, the durability of that response is brief.

“Nothing comes without a cost but many patients are able to receive these drugs and actually do quite well without any major issues.”

Now a new class of drugs are emerging in treating MCC, which offer hope to patients and clinicians because they may be more effective and more easily tolerated for most patients than traditional therapies. They are immunotherapy drugs that specifically block the PD-1/PD-L1 pathway, which cancers use to make themselves invisible to attack by the body’s immune system. Immunotherapies essentially allow the patient’s own immune system to fight cancer. A recent issue of the New England Journal of Medicine, one of the most prestigious peer-reviewed medical journals, published a study in which investigators looked at patients treated with an anti-PD-1 drug as first-line therapy and recorded a high response rate. Similarly, a recent presentation from the American Society of Clinical Oncology 2016 meeting, one of the largest educational and scientific events in the oncology community, described the high response rate in patients first treated with chemotherapy and then with an anti-PD-L1 drug. In comparison to treatment with chemotherapy, generally patients appear to have longer responses and experience fewer side effects.

“It looks like these responses can be durable,” says Dr. Butler. “It’s early days but it looks like they’re durable.”

Allowing the immune system to attack cancer

Cancers are able to evade attack by the immune system through the PD-1/PD-L1 pathway. Breakthrough immunotherapies work by interrupting some of the self-regulatory systems of the immune response. For instance, if an individual is suffering with the flu, a lot of the illness that they are experiencing is due to an activated immune system. To guard against patients becoming severely ill, the immune system has breaks or checkpoints that prevent the immune response from going out of control. Some cancers will utilize the immune system’s natural checkpoints as a way to fend off the immune attack against cancer itself, so anti-PD-1/PD-L1 drugs work by interrupting that regulatory mechanism and allowing the immune system to attack the cancer.

“These immune modulating agents can cause side effects,” says Dr. Butler. “Nothing comes without a cost but many patients are able to receive these drugs and actually do quite well without any major issues.”

The immune system uses multiple mechanisms to activate and inhibit itself and because of the success with using anti-PD-1/PD-L1 drugs to treat not just MCC but many kinds of cancers — lung cancer, melanoma, bladder cancer, and Hodgkin’s lymphoma — researchers are looking at ways to increase the response rate, to figure out why some patients don’t respond as well as others, and to find ways to safely induce higher responses to treatment. The work of the next ten years is to discover ways to boost the body’s immune response to more effectively fight cancer.

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