The jury is still out on the actual benefits of recycling as far as environmental impact but new research suggests that a cellular version could be useful for battling cancer. Scientists at Stanford University have identified a molecule that uses this unexpected pathway to selectively kill cancer cells.
Renal cell carcinoma (RCC), the most common form of kidney cancer, is nearly always caused by mutation of the von Hippel-Lindau (VHL) tumor suppressor gene and often does not respond well to treatment.
The researchers discovered a compound, STF-62247, that was selectively toxic to RCCs deficient in VHL whereas cells with normal VHL were not affected. Treatment of RCC cells lacking functional VHL induced autophagy, a cellular recycling process that cells normally use to conserve resources during times of stress.
"Since RCCs have a poor prognosis and are refractory to standard chemotherapies, there is a need to develop new therapies for kidney cancer," says senior author Dr. Amato J. Giaccia. Dr. Giaccia and colleagues used a sophisticated screening procedure to search for molecules that could selectively destroy VHL-deficient kidney cancer.
"Specifically identifying and targeting the cancer cells, while leaving normal cells intact should have great therapeutic impact. Most side effects people associate with chemotherapy, such as nausea and hair loss, are due to toxic effects of drugs on normal tissues. Exploiting a feature of cancer cells should spare the normal tissue and decrease these awful side effects," explains Dr. Giaccia.
The researchers demonstrated that STF-62247 enhanced autophagy in VHL-deficient cells while inhibition of the autophagy pathway significantly increased the survival of VHL-deficient cells treated with STF-62247. "We have found a small molecule that selectively induces cell death in VHL-deficient cells, such as those that are found in kidney cancer. This represents a paradigm shift for targeted therapy," concludes Dr. Giaccia.
The researchers include Sandra Turcotte, Stanford University School of Medicine, Stanford, CA; Denise A. Chan, Stanford University School of Medicine, Stanford, CA; Patrick D. Sutphin, Stanford University School of Medicine, Stanford, CA; Michael P. Hay, The University of Auckland, Auckland, New Zealand; William A. Denny, The University of Auckland, Auckland, New Zealand; and Amato J. Giaccia, Stanford University School of Medicine, Stanford, CA.