With drug resistance a major challenge in the fight against cancer, a discovery by University of California, Irvine biologists could offer new approaches to overcoming the obstacle. Their research reveals that a mechanism enabling the diseased cells to scavenge dead cell debris for nourishment holds a pivotal role. The paper by Developmental and Cell Biology Professor Aimee Edinger and researcher Vaishali Jayashankar appears in Nature Communications.

“Cancer cells require a tremendous amount of nutrients,” Professor Edinger said. “Chemotherapy and other treatments that damage DNA force tumor cells to rev up their metabolism to make the repairs necessary to survive and grow. Targeting DNA metabolism in this way often works for a while, but in virtually all patients, tumor cells become resistant and the treatment becomes ineffective.”

In probing the problem, the two scientists examined a process called macropinocytosis. It enables a cancer cell desperate for nourishment to scoop up dead cell material within a tumor and feed on it.

“Tumors contain a lot of dead cells because the blood supply is abnormal, causing many cancer cells to starve to death,” Professor Edinger said. “Using this method of scavenging, cancer cells can obtain the amino acids, sugars, fatty acids and nucleotides they require to keep growing.”

This new research revealed that macropinocytosis makes a previously unappreciated contribution to breast cancer drug-resistance. Professor Edinger and Dr. Jayashankar also demonstrated that the same process could thwart treatments for pancreas and prostate cancer.

“What we see is that blocking macropinocytosis can help us to treat many different cancers more effectively,” Professor Edinger said. “This knowledge could enable better biomarker selection in clinical drug trials currently underway, leading to improved response to pharmaceutical combinations. It also provides a strong rationale for developing drugs that target and block macropinocytosis.”

Support for the research was provided by Congressionally Directed Medical Research Programs (CDMRP), the University of California Cancer Research Coordinating Committee, the Chao Family Comprehensive Cancer Center Anti-Cancer Challenge, and UCI Applied Innovation.