Researchers work to control cancer¡¯s evasive actions
BY Ron Gilmore
May 13, 2015
Medically Reviewed | Last reviewed by an MD Anderson Cancer Center medical professional on May 13, 2015
New findings about regulation of PD-L1, a protein that allows cancer to evade the immune system, have shown therapeutic promise for several cancers, including the most common form of lung cancer.
The PD-L1-based therapies inhibit the protein, but they don¡¯t work for everyone. Now, MD Anderson scientists have uncovered more detail about how PD-L1 is regulated by the tumor suppressor gene p53, allowing non-small cell lung cancer to grow.
¡°We identified a novel mechanism by which p53 regulates PD-L1 and tumor immune evasion through control of miR-34a expression,¡± said , associate professor of Radiation Oncology.
P53 is a tumor suppressor gene that, when mutated, promotes tumor growth in many cancers. The microRNA known as miR-34a is a gene commonly found in the lung, and is often missing or under-expressed in tumors.
¡°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 Welsh. ¡°Our study showed that it¡¯s regulated by miR-34a activated by p53.¡±
Understanding more about the mechanics behind these crucial signaling pathways may open up new therapy options for patients. Welsh¡¯s team, which included Maria Angelica Cortez, Ph.D., an instructor in Experimental Radiation Oncology, looked further into how these findings can be tied to existing treatments.
¡°Our results suggest that miR-34a delivery combined with standard therapies, such as radiotherapy, may represent a novel therapeutic approach for lung cancer,¡± said Cortez.
The mouse study found that MRX34, an investigational drug that mimics miR-34¡¯s tumor-suppressing abilities, increased the immune system¡¯s CD8 cells when combined with radiotherapy. A MRX34 clinical trial is currently underway at MD Anderson.
Read the full press release here.