Promising New Lung Cancer Treatment Strategy

Researchers at the Technion’s Faculty of Biology have presented a new strategy that could be used as a treatment for lung cancer. The study, funded by the Israel Cancer Research Fund (ICRF), was led by Prof. Nabieh Ayoub and doctoral student Feras Machour, with contributions from Dr. Enas Rinawi and doctoral student Alma-Sophia Barisaac. Their findings were published in the prestigious journal Nature Communications and their paper was chosen as the Faculty of Biology’s “Article of the Month.”

R to L: Prof. Nabieh Ayoub and Feras Machour

The team investigated the molecular mechanisms that protect cells from DNA damage that can be caused by radiation, smoking, and other factors. When these protective mechanisms fail to repair the damaged DNA, it can lead to cancer development. Therefore, understanding these mechanisms is crucial not only from a scientific perspective but also for developing targeted cancer treatments.

The current research, conducted in collaboration with Prof. Itamar Simon and doctoral student Joyce Kamar from the Hebrew University of Jerusalem, focused on a subtype of lung cancer called lung adenocarcinoma (LUAD). Most LUAD patients are diagnosed at the advanced or metastatic stages when treatment options are limited to surgery, chemotherapy, and other aggressive therapies. However, effective treatment of LUAD remains elusive due to the genetic diversity of the disease and the development of therapeutic resistance. Therefore, the goal of this research was to develop new, personalized treatment strategies for a specific type of LUAD characterized by the loss of RBM10 protein.

In healthy cells, RBM10 functions as a tumor suppressor. Its absence, due to mutations, leads to accelerated cell division and, in some cases, cancer development. The researchers revealed through preclinical experiments that mutations in RBM10 accelerated lung cancer development. Notably, RBM10 loss occurs in approximately 25% of LUAD patients and confers resistance to current treatments.

To identify targeted therapies against RBM10-deficient cancers, the researchers conducted extensive genomic screening that identified 60 genes that could serve as effective therapeutic targets in lung cancer with RBM10 mutations. Among these 60 genes, the researchers focused on the WEE1 gene, since drugs that inhibit it are currently undergoing clinical trials for cancer treatment. The researchers demonstrated that WEE1 inhibition is highly effective in eradicating RBM10-deficient lung cancer in mice and therefore can be harnessed therapeutically with immediate clinical applicability.

To read the full article: https://www.nature.com/articles/s41467-024-50882-0