Cross-talk between macrophages and tumor cells could modulate cachexia in pancreatic cancer patients. A group of scientists from the University of Oklahoma has discovered a new pathway that promoted muscle wasting after the recruitment of this immune cell in the tumor microenvironment, activating cachexia-inducing factors. Macrophage depletion and the inhibition of this signaling could be developed as a therapeutic target for this condition.
Many patients with cancer in advanced stages develop cachexia, a metabolic disorder characterized by systemic weight loss and muscle and adipose tissue wasting.
With a sizeable series B financing well underway, Actimed Therapeutics Ltd. is preparing to advance its compound, S-pindolol benzoate (ACM-001), into a phase IIb/III trial to treat cachexia secondary to colorectal cancer, having also recently completed a £4.75 million (US$5 million) series A extension round.
Cancer cachexia is a collection of symptoms involving progressive bodyweight loss with associated depletion of liver and skeletal muscle energy that ultimately bodes a poor prognosis in patients with cancer. Cachexia occurs in approximately 80% of patients with advanced cancer, and it is the most significant independent negative predictor of death with ~30% of cancer patients dying of cachexia. There are currently no effective treatments for cancer cachexia.
CSPC Pharmaceutical Group Ltd. has announced clinical trial approval by China’s National Medical Products Administration (NMPA) for the antibody drug JMT-203, being developed by the company’s Shanghai JMT-Bio Technology Co. Ltd. subsidiary for cancer cachexia.
Blocking signaling through the ectodysplasin A2 receptor (EDA2R), a member of the TNF receptor family, protected tumor-bearing mice from developing muscle atrophy associated with cancer cachexia. Upstream and downstream of EDA2R, “we identified two distinct pathways and we demonstrated their involvement in muscle wasting,” Serkan Kir told BioWorld. Kir is a professor at the Koç University Center for Translational Medicine and corresponding author of the paper reporting the findings, which appeared in Nature on May 10, 2023.
The most comprehensive study to date of how lung cancer evolves in response to selection pressures indicates the genetic profile at diagnosis can be used to predict how a tumor is likely to progress, opening up new prospects for personalized medicine and potential therapeutic targets. The data were generated in Tracerx (Tracking cancer evolution through therapy), a £14 million (US$17.4 million) study funded by the charity Cancer Research UK (CRUK) with the aim of defining how clonal heterogeneity of tumor cells affects the risk of recurrence and survival.
Researchers at the Dana-Farber Cancer Institute have been able to identify proteins that were released from muscles during exercise in relatively small quantities. Using their method, the team was able to demonstrate that the neurotrophic factor prosaposin was produced during exercise. Prosaposin is “a well-known CNS neurotrophic factor, but has never been seen to come out of muscle or fat,” Bruce Spiegelman told BioWorld. Spiegelman is a researcher at the Dana-Farber Cancer Institute and Stanley J. Korsmeyer Professor of Cell Biology and Medicine at Harvard Medical School.
Investigators working at University of Texas Health Science Center, Houston, have discovered that the ubiquitin ligase UBR2 is up-regulated and sufficient for targeting the myosin heavy chain protein for the degradation characteristic of cancer cachexia. UBR2 knockout or pharmacological inhibition could prevent cachexia in mice. Confirmatory observations were noted in cancer cachexia patient-derived tissues.
Wellstat Therapeutics Corp. has described compounds for co-delivery of uridine and ketoleucine with high bioavailability reported to be useful for the treatment of muscle atrophy, sarcopenia and cachexia.
