Gene Mutations

Cancer, About one-fifth of often fatal head and neck cancers have genetic mutations in a pathway important for normal cell growth, according to scientists, and those mutations, which allow abnormal cancer cell growth, can also make cancer vulnerable. Individualized genomic analysis to identify a patient’s specific mutation and finding drugs that directly target it are keys to targeting that vulnerability, they report in a review article published in the journal NPJ Genomic Medicine.

According to Dr. Vivian Wai Yan Lui, molecular pharmacologist and translational scientist at the Georgia Cancer Center and Medical College of Georgia and the paper’s corresponding author, the MAPK pathway is a “signaling hub” for cells important to the normal development of the head and neck region, and activating key pathway constituents, such as the genes MAPK1 and HRAS, is known to drive the growth of a variety of cancers.

Gene mutations that contribute to head and neck cancer also provide ' precision' treatment targets – Jagwire

However, mutations in the MAPK pathway genes that enable tumour growth can also make it sensitive to drug therapy, according to Lui. While more research is needed to identify additional mutations in the MAPK pathway and drugs that target them, Lui believes they are among the most logical treatment targets for this difficult-to-treat cancer. She is looking in her lab for drugs that kill head and neck primary tumours from patients, as well as the genetics behind how they kill, as she speaks.

According to Lui, erlotinib failed in clinical trials because it was not given to the right patients, which is what precision medicine is. Indeed, she claims that laboratory studies have shown that activation of MAPK1 confers resistance to erlotinib, whereas this patient’s response clearly contradicts that. Grandis’ follow-up research revealed that the higher the MAPK1 activation in patients, the better the cancer responded to erlotinib.

To help advance cancer treatment, Lui encourages doctors who encounter these “exceptional responses” to report them, collaborate with scientists to study them, and then pursue clinical trials when appropriate.

Her message to patients is not to give up because, with more high-level tumour analysis, there may be a specific mutation that makes their cancer vulnerable to a specific medication, she says of these “gene-drug responses” that are the focus of her translational work.”There are secrets that expose the cancer,” Lui says. “When cancer cells have an important gene mutation that they are activating or that cancer cells are addicted to for survival, when you hit that signalling pathway, the cancer cells die or are very well controlled.”

Prior to the era of genomic medicine, when scientists discovered and targeted specific gene mutations, “non-precision” drug treatment of the MAPK pathway in head and neck cancers and other cancers was “futile,” and typically “failed miserably” in clinical trials, according to Lui and her colleagues.

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