Killing latent tumors before they can grow back
Standard treatment for brain tumors includes chemotherapy and radiation. These slow tumor growth by inducing a state of "senescence," which is a survival mode for damaged cells that are no longer dividing. Senescent cells also accumulate during aging, and new drugs, called "senolytics" are showing promise to eliminate these damaged cells and the disease of aging that may owe their existence to the abnormal signals produced by senescent cells. We are collaborating with senescence experts to understand what senescent tumor cells look like and how we can take advantage of this unique "window of opportunity" to potentially kill residual senescent tumor cells after chemoradiation prior to tumor recurrence.
So far, we have found that Bcl-XL is a potentially promising target, since senescent glioma cells are more dependent on this pro-survival signal than non-senescent cells.
Rahman M, Olson I, Mansour M, Carlstrom LP, Sutiwisesak R, Saber R, Rajani K, Warrington AE, Howard A, Schroeder M, Chen S, Decker PA, Sananikone EF, Zhu Y, Parney IF, Burma S, Brown D, Rodriguez M, Sarkaria JN, Kirkland J, Burns TC. Selective vulnerability of senescent glioblastoma cells to Bcl-XL inhibition. bioRxiv; preprint. 2020; 10.1101/2020.06.03.132712.
We have started a clinical trial offering surgery for patients with residual latent tumor. Although tumors hare normally only removed when they are growing, we believe that having less residual tumor, even after prior treatment, should decrease the risk of recurrence. By removing "latent" brain tumors prior to recurrence, we hope to improve survival, and also learn from these valuable human tumor samples to understand how best to target them with novel therapies.
A study to evaluate the surgical removal of residual brain tumors prior to recurrence.