An important part of the immune system is its ability to tell between normal cells in the body and those it sees as “foreign.” When the immune system is able to detect foreign cells, it can attack just those cells while leaving the normal cells alone. To do this, it uses “checkpoints” – molecules on certain immune cells that need to be activated (or inactivated) to prompt an immune response.
New Kind of Drug
Checkpoint inhibitors are a relatively new class of cancer drugs – often made of antibodies – that can direct an immune system attack on cancer cells. The drugs have had some impressive successes in recent years, particularly in patients with metastatic melanoma or Hodgkin lymphoma, and are showing promise in clinical trials involving patients with other types of cancer.
Research has shown that cancer cells often hijack immune system checkpoint molecules to suppress and evade an immune system attack. T cells, the cells that attack dangerous cells, are deceived by these normal-looking proteins and can allow the tumor cell to go unchecked. Checkpoint inhibitors block these deceptively normal-looking proteins on cancer cells, triggering an immune system assault on them.
There is growing excitement about the potential of immunotherapy treatments for multiple types of cancer. At the 2015 meeting of the American Association for Cancer Research (AACR), one of the largest cancer research meetings in the United States, investigators from the Dana-Farber Cancer Institute presented encouraging results of immunotherapy for melanoma, lung cancer, and breast cancer.
As a result of these and other studies, immunotherapy continues to be one of the fastest-evolving fields in oncology. Efforts are underway to develop checkpoint inhibitor medications for kidney cancer, bladder cancer, neck and head cancers, breast, and ovarian cancers. Many immunotherapies have shown good efficacy, safety, and durability across many tumor types, including some advanced solid tumors that have not seen meaningful treatment developments in decades.
Checkpoint inhibitor therapy is also showing promise treating blood cancers myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Early research reported at the 2016 Chemotherapy Foundation Symposium into the viability of checkpoint inhibitors in blood cancers focused on finding which checkpoints show the most activity. Phase I studies suggest a strong trend toward successful treatment though the data is still immature and the patient population was small.
Immunotherapy changes the cancer fight from trying to use drugs to kill cancer cells through chemotherapy and radiation to using drugs to enable the patient’s body to attack malignant cells. Chemotherapy and radiation side effects arise because the treatments are designed to kill fast-growing cells, and inevitably miss the mark, killing healthy cells that cause painful and uncomfortable side effects.
Not that checkpoint inhibitors are without side effects. Many of the observed “adverse events” in patients using checkpoint inhibitors are mild, or low-grade, such as skin rashes and intestinal discomfort. Some more serious side effects seen have been inflammation of the lungs, bowel, pancreas and liver.
Research is still in the early stages, and there is hope that the side effects can be mitigated as the science matures. Announcing a market research report on checkpoint inhibitors for urological cancers, GBI Research Associate Analyst Adam Bradbury said, “Over the past five years, immune checkpoint inhibitor trials have reported strong clinical data in many tumor types across oncology, including melanoma, kidney cancer, colorectal cancer, and non-small cell lung cancer. This treatment group’s uptake is predicted to be considerable due to the relatively high toxicity associated with chemotherapy agents and the typically poor performance status of many elderly patients, which necessitates the use of less-toxic targeted therapies.”
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