The discovery of proteins that initiate the muscle wasting caused by tumors could lead to new treatments for this hard-to-treat and often fatal condition called cancer-induced cachexia or cancer cachexia, report scientists with the McGovern Medical School in a proof-of-concept study in the journal Nature Communications.
Cancer cachexia is a wasting syndrome that causes weight loss and inflammation and can reduce the effectiveness of cancer drugs while in turn increasing their harmfulness. Approximately half of all cancer patients will develop this condition, and about half of the patients with cachexia will die of it before their cancer treatment has a chance to kill the cancer.
The National Cancer Institute issued a “Provocative Question” to the scientific community several years ago: “What mechanisms initiate or sustain cancer cachexia, and can we target them to extend lifespan and quality of life for cancer patients?”
In an effort to answer this question, UTHealth researchers found that in mouse cancer models, when they blocked the activity of the proteins named Hsp70 and Hsp90 in the bloodstream, the development of cancer cachexia stalled. The researchers used antibodies to neutralize the proteins in one model and silenced the genes that create them in cancer cells in another.
“We are the first to link elevated serum levels of Hsp70 and Hsp90 to cachexia in mice, and show that these proteins drive both muscle wasting and inflammation,” said Yi-Ping Li, Ph.D., the senior author and a professor of integrative biology and pharmacology at McGovern Medical School at UTHealth. “These proteins are promising therapeutic targets for defeating cachexia.”
Cancer cachexia primarily occurs in solid tumors including lung, pancreatic, colorectal and gastric cancer. “We show that all of these tumor cells from humans release high levels of Hsp70 and Hsp90, which explains the previous clinical findings that patients with these tumors tend to have elevated serum levels of these proteins,” Li added.
The next step in the research will involve investigations on cancer patients to determine if these proteins are biomarkers of cancer cachexia in humans, Li said.
Li said their findings could help in the understanding of other conditions that cause muscle loss such as chronic obstructive pulmonary disease and congestive heart failure, where circulating Hsp70 is also elevated.
The paper, “Tumor induces muscle wasting in mice through releasing extracellular Hsp70 and Hsp90,” was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases grant (AR063786).
The paper’s first author, Guohua Zhang, Ph.D., is an assistant professor of integrative biology and pharmacology at McGovern Medical School. UTHealth coauthors include Yong Zhou, Ph.D.; Ka Wai Thomas Sin, Ph.D.; Zhiren Zhu; Rene Flores, Ph.D.; and Qingyun “Jim” Liu, Ph.D.
Liu is the Janice Davis Gordon Chair for Bowel Cancer Research at UTHealth, and is on the faculty of The University of Texas MD Anderson UTHealth Graduate School of Biomedical Sciences along with Li.