Targeting Lung Cancer From a New Direction

Debu Tripathy, M.D.

Targeted therapies have made a huge impact on the treatment of cancer over the past couple of decades. Making a breakthrough in the 1980s, they work to identify and attack specific types of cancer cells by interfering with specific proteins that drive the growth of cancer cells. Doctors can test for these molecules, also known as molecular targets, by taking cells through tissue or liquid biopsies.

The first Food and Drug Administration (FDA)-approved targeted therapy for lung cancer, specifically, came in 2004 with Avastin (bevacizumab), which inhibits a protein that leads to tumor-associated blood vessels and is currently used to treat advanced colorectal, kidney and lung cancers. Additionally, there has been an explosion of knowledge from sequencing the DNA of many different cancer types to discover the many genes that are mutated, and the proteins encoded by these genes can drive tumor growth.

In this issue of CURE®, we explore targeted therapies further as they pertain to the human epidermal growth factor receptor 2 (HER2) protein in non-small cell lung cancer (NSCLC), which can be mutated or amplified in several tumor types and promotes cancer cell growth. This mutation affects about 2% to 4% of patients with NSCLC.

Of note, there is only one FDA-approved targeted therapy for the patient subset. Called Enhertu (trastuzumab deruxtecan), the drug treats patients with metastatic NSCLC that has progressed on chemotherapy. One expert featured in our issue hopes more targeted therapies for HER2 will be approved to give patients more personalized options. With this said, there are more targeted therapy drugs in clinical trials that could help this patient population. One such drug is a tyrosine kinase inhibitor called poziotinib, which targets the HER2 exon 20 insertion mutation. In our feature, we speak to a patient who enrolled in a phase 2 trial of the drug and has been participating since April 2021. While she has experienced some moderate side effects from the therapy, she is optimistic, as other treatment options led to either severe side effects or disease progression.

Highlighting the importance of participation in clinical trials, it is my hope that this field continues to grow the novel therapy for not only patients with lung cancer, but well beyond. It is critical that the public be aware of how research and clinical trials are catalysts to better the outcomes of patients with cancer.

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