Researchers at the University of Pennsylvania School of Medicine may have found a way to turn an adaptive cellular response into a liability for cancer cells. When normal cells are starved for food, they chew up existing proteins and membranes to stay alive. Cancer cells have corrupted that process, called autophagy, using it to survive when they run out of nutrients and to evade death after damage from chemotherapy and other sources.  When the Penn investigators treated a group of patients with several different types of advanced cancers with temsirolimus, a molecularly targeted cancer drug that blocks nutrient uptake, plus hydroxychloroquine, an anti-malarial drug that inhibits autophagy, they saw that tumors stopped growing in two-thirds of the patients.

“The results are very encouraging -- striking, even” says senior author Ravi Amaravadi, MD, an assistant professor of Medicine at Penn’s Abramson Cancer Center. “Temsirolimus by itself has little effect in this patient population. Tumors laugh at it, with response percentages of just zero to 5 percent. But by combining it with hydroxychloroquine, we found that 14 out of 21 patients had stable disease after treatment, including five out of six melanoma patients.”

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