Weight loss and a dramatic wasting of muscle mass sadly is part of having cancer for many individuals. Known as “cachexia” (ku-KEK-see-uh), the condition is complicated, little talked about, and can get lost in the competing pressures oncologists and their patients face.
Many people have never heard of cachexia, a word with roots in a Greek term for “bad condition.” But a global funding initiative known as Cancer Grand Challenges announced today that it is supporting four diverse worldwide communities of researchers with $25 million each, to come together, think differently, and take on cachexia and some of cancer’s other tough challenges.
Wilmot Cancer Institute scientists Karen Mustian, Ph.D. M.P.H., Richard Dunne, M.D., and Po-Ju Lin, Ph.D., M.P.H., are part of one of the Cancer Grand Challenges global teams. The Wilmot scientists will conduct clinical and translational research to improve the understanding of cancer cachexia and develop therapies. The University of Rochester Medical Center will receive approximately $2.6 million as part of this collaborative effort.
The global cachexia team is spread across 14 institutions and led by scientists at Rutgers Cancer Institute of New Jersey, Weill Cornell Medicine, and Cold Spring Harbor Laboratory. In addition to URMC, it includes researchers at Kaiser Permanente Medical Program of Northern California, Cancer Research UK Beatson Institute, Cancer Research UK Cambridge Institute, The Salk Institute for Biological Studies, Harvard Medical School, Harvard T.H. Chan School of Public Health, Louisiana State University, University of Cambridge, University College London, and University of Glasgow.
“What’s wonderful about the Cancer Grand Challenges program is that it forms ‘dream teams’ of researchers to investigate pervasive problems on a large scale,” said Mustian, who is also a dean’s professor of Surgery at UR Medicine. “It brings together a group of multidisciplinary scientists that wouldn’t have gotten together but for this award.”
Dunne, an assistant professor of Hematology/Oncology in the Department of Medicine, treats people with gastrointestinal cancers who are prone to cachexia. Currently, there is no one-size-fits-all approach to managing it and no FDA-approved therapies, although a few treatments have been under study in clinical trials.
“I think the field of cachexia is on the brink of some big findings,” Dunne said. “Much effort up until now has furthered our understanding of this condition but has not yielded new approvals for therapeutic strategies. This effort will push us to turn things around.”
Cancer Grand Challenges was founded by the National Cancer Institute (part of the National Institutes of Health) and Cancer Research UK, a non-profit and the world’s largest cancer charity. Together they’ve invested $100 million in the teams announced today.
“I am over the moon about what we may be able to discover together as a large team, and the fast pace at which we will be able to make real change,” Mustian said. “We are honored that Wilmot investigators are part of this incredible group of eminent scientists from across the world.”
What is Cachexia?
The cellular mechanisms are unknown, but the condition has been characterized as having three stages: pre-cancer treatment, present, and resistant or recurring cachexia. Managing it is harder in advanced stages. Few studies have followed people with cachexia long-term, and scientists have not reported reliable biomarkers for early detection.
Chemotherapy is known to speed weight and muscle loss, and some researchers believe that tumor cells release substances that reduce appetite.
What is certain? It is a major source of emotional stress for patients, families and caregivers.
“It causes friction when patients say they are not hungry and just cannot eat,” Dunne said. “I try to assure people that it’s not their fault.”
At Wilmot, patients with cachexia are managed by oncologists, nurses, and registered dieticians, and that will continue as Mustian, Dunne and Lin work with the Cancer Grand Challenges group to make progress. Dunne recently ran two clinical trials, looking at whether exercise and a smoothie-like nutritional supplement with whey protein, vitamin D, and high doses of omega 3 fatty acids, can boost people with cachexia. He expects to have results later this year.
The Grand Challenge
The global collaboration unites clinicians, advocates, and scientists with expertise in cancer, metabolism, neuroendocrine function, immunology and more, to build a virtual cachexia research center. Winning a Cancer Grand Challenges grant is extremely competitive: Nearly 170 teams submitted proposals, and reviewers narrowed that group to 11 before the final four teams were selected.
The cachexia team has three sub-teams that will study basic molecular mechanisms. The fourth team is based out of Wilmot and Kaiser Permanente in California, and will conduct the largest clinical trial to date for cancer cachexia to study the natural progression of the condition and its biological underpinnings. Wilmot investigators will also build a large bank of bio-specimens devoted exclusively to studying whether the laboratory findings from bench scientists can be transferred to humans.
To achieve this, Mustian, Dunne, and Lin are also recruiting 800 individuals across the U.S. who suffer from cachexia for the clinical trial. Patients will volunteer to be observed and to submit tumor samples, blood, and precise measurements of muscle mass and functional abilities over time. The Wilmot team will leverage its status as an NCI Community Oncology Research Base (NCORP RB), which Mustian also leads, enabling access to patients locally and at hundreds of community cancer clinics across the country.
“The projects of our bench science colleagues will inform our work, and our projects will inform theirs,” Mustian said. Having human blood and tissue samples readily available, for instance, could fast-track the discovery of new biomarkers and treatment options.
Mustian, an exercise physiologist and co-leader of Wilmot’s Cancer Prevention and Control research program, predicts that scientists may find that movement can help some people with cachexia. Lin, a research assistant professor of Surgery, also has expertise in exercise oncology, behavioral medicine, and supportive care in cancer. Her participation involves collecting data on psychosocial characteristics, and conducting functional assessments and dietary evaluations for patients with cachexia.
“There is so much variability to this condition,” Mustian said. “Some people have weight loss but not as much functional loss and others lose muscle mass and may have a predisposing genetic condition. We have many questions to answer.”
Rochester has a long, successful history of research into the side effects and toxicities associated with cancer and its treatment — with cachexia being the latest effort.
For example, decades ago cancer-related nausea was poorly understood and impacted survival. But pioneering discoveries made in Rochester led to drugs to control nausea, allowing patients to finish their treatment regimens.
“If better treatments for cachexia are developed,” Dunne said, “patients will get stronger and hopefully, live better, more fulfilling lives during their cancer treatment and beyond.”