a gene would be linked to the disease

THE ESSENTIAL

• Lung cancer is the third most common cancer in Europe.
• Squamous cell carcinoma of the lung develops in the cells that line the airways.

The lung cancer can take several forms. There are two main groups: small cell lung cancers and non-small cell lung cancers. This second category includes 80% of lung cancer cases. Squamous cell carcinoma belongs to this type of cancer. In France, it represents regarding 30% of cases. If tobacco remains the main cause, other factors may explain its appearance. In the review Cancer Cella research team points to the responsibility of certain genetic variations.

Lung cancer: the deletion of a gene in question

Scientists at the Perlmutter Cancer Center in New York have identified a gene associated with the development of this form of lung cancer. According to their conclusions, the deletion of the KMT2D gene causes the transformation of normal lung cells into cancerous cells in cultures of cells called organoids. “Our study identifies KMT2D as a critical contributor to the development of squamous cell lung cancers and offers vital clues on how to target KMT2D-deficient lung squamous cell carcinomas“says one of the study’s authors Kwok Kin-Wong.

KMT2D’s role is to regulate the activity of genes that enable the construction of enzymes capable of limiting cell growth-stimulating signals sent by another set of enzymes called receptor tyrosine kinases (RTKs). Two RTKs, called EGFR and ERBB2, are known to participate in the abnormal activation of a signaling pathway that leads to the continuous multiplication of cancer cells.

Lung cancer: a future treatment targeting the KMT2D gene?

The research team tested their hypotheses on mouse. Specifically, she observed the effects of two potential drugs: the SHP2 inhibitor SHP099 and the pan-ERBB inhibitor afatinib. Used together, they would make it possible to compensate for the deficit in KMT2D, according to the authors. In any case, the experiment confirmed the role of KMT2D: the combination of the two drugs slowed the growth of lung tumors in mice with squamous cell carcinoma of the lung, which had been genetically modified to lack KMT2D.

“Several SHP2 inhibitors are currently being tested in clinical trials, and afatinib is already available“, warns Hua Zhang, MD, co-author. For the team, the results obtained justify the initiation of clinical trials in KMT2D-deficient patients with squamous cell carcinoma of the lung. There is no treatment that specifically targets this type of cancer.