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Cancer scientists identify new target drug for several types of tumors

UC Cancer Scientists in San Diego Identify New Target Drug for Multiple Types of Tumors

Electron micrograph in false color of two cancer cells. Credit: Thomas Deerinck, National Research Center for Microscopy and Imaging, UC San Diego.

A research team led by scientists from the University of California San Diego School of Medicine and the Ludwig Institute of Cancer Research at the University of San Diego identified an enzyme involved in the remodeling of the plasma membrane of several types of cancer cells, essential for tumor survival and survival. their uncontrolled growth.

The conclusion, published in the July 11, 2019 issue of Cell metabolism, suggests a potential target for new drugs.

"Cancers are characterized not only by major changes in their genomes, but also by profound changes in the way they absorb and use nutrients to drive rapid tumor growth," said lead author Paul S. Mischel, MD , professor at UC University of San Diego. Department of Pathology Medicine and Member Ludwig. "How are these various aspects compatible and can they be exploited for the benefit of patients?"

In the new study, conducted in collaboration with Benjamin Cravatt, Ph.D., professor at Scripps Research and led by first author Junfeng Bi, Ph.D., in Mischel's lab, the researchers identified an enzyme called LPCAT1, whose levels increase cancer and which plays a key role in tumor growth by altering the phospholipid composition of the plasma membrane of cancer cells, thus allowing amplified and mutated growth factor signals to stimulate tumor growth.

Without LPCAT1, tumors can not survive. When researchers genetically depleted LPCAT1 in many types of cancer in mice, including highly deadly glioblastomas (brain) and aggressive lung cancer, malignancies have decreased dramatically and survival times have improved.

The results, the authors write, demonstrate that LPCAT1 is an important enzyme that becomes dysregulated by cancer, linking common genetic alterations of tumors to changes in their metabolism to stimulate aggressive tumor growth. "

"Advances in DNA sequencing technologies have redefined our understanding of the molecular basis of cancer, suggesting a new, more effective way to treat cancer patients," said Mischel. "However, to date, precision oncology has not yet benefitted many patients, prompting further research to understand how genetic alterations in tumors alter the behavior of cancer cells and could lead to new ways of treating patients more effectively.

"These results also suggest that LPCAT1 could be a very convincing new drug target in a wide variety of cancer types."

Exposing the metabolic dependencies of cancer

More information:
Junfeng Bi et al, Oncogenic amplification in growth factor signaling pathways makes cancers dependent on remodeling of membrane lipids, Cell metabolism (2019). DOI: 10.1016 / j.cmet.2019.06.014

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