• Michael Misialek, MD

Immunotherapy in Lung Cancer

November is National Lung Cancer Awareness Month. Lung cancer is the second most common cancer in both women and men, accounting for 13% of all new cancers. The American Cancer Society estimates that in 2015 in the United States there will be about 221,200 new cases of lung cancer with an estimated 158,040 deaths.

What is immunotherapy?

The advent of precision medicine has ushered in a new way of battling cancer. With an understanding of the genetics of cancer, treatment is now personalized specific to a patient's unique tumor characteristics. However, one of the limitations of precision medicine is the inevitable development of treatment resistance by the tumor. The vast majority of patients, after experiencing clinical benefit, will require a change in treatment as their tumor mutates. As a cancer changes, so must our response. In this perennial "cat and mouse" game, new approaches must be developed to keep up.

Instead of always playing "catch up" with a tumor, immunotherapy offers the greatest hope in our search for a cancer cure. By harnessing the power of the immune system, the body can keep up with new mutations. What is cancer immunotherapy?

Immunotherapy can be broken into 3 major categories: monoclonal antibodies, vaccines and nonspecific immunotherapies. Antibodies are the body’s ammunition against cancer. In the lab, antibodies can be produced specific to a patient’s tumor. These are then injected into a patient.

Vaccines are also a promising area of research. Already we have effective vaccines against some cancers. There are vaccines for HPV, which protects against cervical cancer, and hepatitis B, which protects against liver cancer. Vaccines are also being developed to treat cancer. Recently an effective vaccine against metastatic prostate cancer was approved (Provenge).

Finally, nonspecific immunotherapies are one of the hottest areas in cancer research currently. These can be divided into:

Cytokines – These are molecules which stimulate the immune system. Checkpoint inhibitors – These release the brakes on the immune system, i.e. PD-1/PD-L1 PARP inhibitors. Immunomodulating drugs – Cause a boost to the immune system, i.e. Thalidomide

Lung cancer immunotherapy

Nivolumab (Opdivo) and pembrolizumab (Keytruda) target PD-1, a protein on T cells that is important in recognizing other cells. When PD-1 is blocked, the immune system “brakes” are released and the T cell response against cancer is boosted. These drugs have been shown to shrink some tumors or slow their growth. Both drugs have been approved for patients with non-small cell lung cancer as a second line treatment after tumor begins to grow after standard chemotherapy.

Pathologist’s role

Pathologists are involved in each step of the process. First, a tumor may be biopsied in either the operating room or radiology under CAT scan guidance. Pathologists are called upon to assess the sample, ensuring it is adequate for both diagnosis and testing for precision medicine targets (“actionable mutations”).

In the lab, pathologists examine tissues under the microscope using various stains to make a diagnosis. When appropriate, a tumor is tested for the presence of “actionable mutations”. If discovered, the patient may be eligible for targeted therapy. The success of precision medicine depends on pathologists.

Follow Path Report during November as we celebrate National Lung and Pancreatic Cancer Awareness. See how pathologists are crucial members of the care team.

#lungcancer #pathology #immunotherapy #precisionmedicine

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