HEAD AND NECK CANCER: Guilty mutations remain the best targets

HEAD AND NECK CANCER: Guilty mutations remain the best targets

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About 20% of often fatal cancers of the head and neck harbor genetic mutations in one of the essential pathways for cell growth and these scientists explain to us that these mutations, which incidentally allow abnormal growth of cancer cells too, can constitute the very key to their vulnerability.

Growth keys, vulnerability keys

Growth paths: the MAPK pathway is a “signaling hub” for cells important for normal development in the head and neck region, and activation of key constituents of the pathway, such as the MAPK1 and HRAS genes, is known to stimulate the growth of a variety of cancers, explains one of the lead authors, Dr. Vivian Wai Yan Lui, a molecular pharmacologist and researcher at the Georgia Cancer Center and the Medical College of Georgia.

A clinical case: The team’s interest in the MAPK pathway began a decade ago at the University of Pittsburgh where one of the lead authors, Dr. Vivian Wai Yan was studying head and neck cancer. . A patient in his 30s, a heavy smoker and drinker, had stage 4 head and neck squamous cell carcinoma that had metastasized to his lymph nodes. Then still naïve to treatment, he had received, for 13 days, a drug (erlotinib) blocking the epidermal growth factor receptor, or EGFR, involved in cell growth, and abundantly expressed during rapid tumor growth. During the surgery, the surgeon had then reported that there was no cancer on his tongue or in his lymph nodes… The response was then described as an “exceptional response”, suggesting that targeting certain mutations in particular could also inhibit the growth of tumor cells – here “dependent” on the mutated EGFR signal.

Vulnerability pathways: the same mutations in the MAPK pathway genes that enable tumor growth may therefore also render it responsive to drug therapy. From there, we will have to identify more mutations in the MAPK pathway and the drugs that target them, explain the researchers: “Each type of cancer probably has one or more drug-sensitizing mutations that can vary among patients depending on how they got their cancer.”

What methodology? The team is building panels of genes that will help accelerate the discovery of targets in this very heterogeneous cancer. Other centers are also conducting clinical trials around the world to identify these specific mutations and the drugs that precisely target them. Then, the researchers call their colleagues who “encounter” such exceptional responses to share these clinical cases. Next, the goal will be to combine this “precision medicine” approach with immunotherapy that induces a patient’s immune system to better target the cancer as well.

What implications for patients? The message for patients is to “don’t give up” because with further analysis of tumors there are mutations responsible for tumor growth that make their cancer vulnerable to a specific drug.

Genomic medicine, which today makes it possible to identify and target a specific genetic mutation, opens up a new, broad and promising avenue for a large number of cancers for which there are currently no or few treatments.

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