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 study by Aimee Edinger, associate professor of developmental & cell biology, and researcher Vaishali Jayashankar appears in Nature Communications.
“Cancer cells require a tremendous amount of nutrients,” 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,” 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. Edinger and 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,” 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.
About the University of California, Irvine: Founded in 1965, UCI is the youngest member of the prestigious Association of American Universities. The campus has produced three Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 222 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $5 billion annually to the local economy. For more on UCI, visit www.uci.edu.
Reference: Jayashankar, V., Edinger, A.L. (2020) Macropinocytosis confers resistance to therapies targeting cancer anabolism. Nat Commun. DOI: https://doi.org/10.1038/s41467-020-14928-3
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