miR-34a Shown To Be a Promising Target In Lung Cancer Therapy

miR-34a Shown To Be a Promising Target In Lung Cancer Therapy

Researchers from The University of Texas MD Anderson Cancer Center have uncovered the mechanism by which the tumor suppressor gene p53 regulates the molecule programmed cell death protein 1 (PD-L1) in small cell lung cancer. The study entitled “p53 regulation of PDL1 is mediated through miR-34a” was presented during the 2015 American Association for Cancer Research (AACR) Annual Meeting in Philadelphia, PA.

Clinical studies have tested promising therapies for several types of cancer, including non-small cell lung cancer (NSCLC), by targeting PD1/PDL1 signaling, a pathway that contributes to the immune evasion of cancer. However, the regulation of PDL1 expression is not well understood. Notably, the treatment inhibiting the PD-L1 protein does not function for all patients.

The authors had previously found that the microRNAs 200 (miR-200s) family directly regulates PDL1. The miR-200s family has been found to be deregulated in several types of cancers, where they have a crucial role in tumor initiation, maintenance, malignant metastasis and chemotherapy resistance.

James Welsh, M.D., senior author of the study, said in a news release that the team identified a new mechanism by which p53 regulates PD-L1 and tumor immune evasion through the regulation of miR-34a expression.

The mutated tumor suppressor gene p53 is involved in the growth of several tumors and miR-34a is a gene frequently observed in the lung but in situations of cancer, it is normally absent or expressed at low levels. “Although clinical studies have shown promise for targeting PD-1/PD-L1 signaling in non-small cell lung cancer, little is known about how PD-L1 expression is regulated,” said Dr. Welsh, who added that PD-L1 expression is regulated by miR-34a which in turn is activated by p53.

“Our results suggest that miR-34a delivery combined with standard therapies, such as radiotherapy, may represent a novel therapeutic approach for lung cancer,” said Dr. Angelica Cortez, first author of the study.

A better understanding of the regulation mechanism of the PD1/PDL1 signaling pathway will contribute to the development of novel treatments for cancer patients. Overall, this study suggested that delivery of miR-34a to cancer cells in combination with standard therapies, such as radiotherapy, may be a new potential therapeutic strategy for lung cancer.

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