Targeting Gene Offers Promise for Developing Melanoma Treatments
A recent study published in the journal Nature Communications has discovered that a gene previously implicated in blood vessel formation during embryonic development and tumor growth also induces immune suppression during tumor development. This novel finding, published April 29, suggests a new avenue for developing therapeutic approaches in treating patients with melanoma and other advanced-staged cancers.
The current study expands our understanding of how of a gene called Inhibitor of Differentiation 1 (Id1) contributes to tumor progression. About 20 years ago, researchers discovered that Id1, which is normally present in embryos, was also present in cancer patients. Increased Id1 protein expression in tumors has been shown to correlate with both cancer progression and poor prognosis. The present study reveals that when a tumor-secreted protein called transforming growth factor beta (TGFβ) promotes the activation of Id1, the normal pathway in immune cell development is hijacked and interferes with the entire immune system, starting in the bone marrow. This dual immunosuppressive and pro-metastatic mechanism provides an optimal environment for cancer to grow, spread and thrive.
Despite the well-documented evidence suggesting that malignant melanoma is an immunogenic tumor, clinical outcomes for immunotherapeutic strategies have not been as promising as anticipated. Given the rise in incidence and death rates of metastatic melanoma, there is increased urgency for a deeper understanding of the regulation of these pro-metastatic, immunosuppressive mechanisms.
Advanced melanoma patients express higher levels of Id1 in myeloid peripheral blood cells. This new discovery confirms and extends the promise of Id1 as a biomarker of cancer progression and as a therapeutic target in the management of advanced malignancies.
“Targeting Id1 offers the potential to restore overall immune function,” said senior author Dr. David Lyden, the Stavros S. Niarchos Professor in Pediatric Cardiology and a professor of pediatrics in the Department of Pediatrics at Weill Cornell Medical College. “When the immune system is functioning, treatment options are more plentiful.”
Targeting Id1 might provide a three-pronged therapeutic approach, which would first reduce the metastatic potential of the tumor itself, then reduce the tumor’s ability to form new blood vessels, a process called vasculogenesis, and finally restore the patient’s systemic immune function.
By: Wendy Meltzer, MPH
[Image by Cliff]