Bonetto Lab
The Bonetto Lab at University of Colorado Anschutz Medical Campus investigates the molecular causes responsible for the onset of muscle and bone complications in cancer (i.e., cachexia). Up to 80 percent of patients diagnosed with advanced cancers will develop cachexia, accompanied by progressive body weight loss. This condition is estimated to cause up to 30 percent of cancer deaths, which also means that a third of cancer patients are expected to die OF cachexia rather than WITH cachexia. Cancer cachexia is more frequently diagnosed in patients with certain types of cancer, especially pancreatic and gastric cancer, lung, esophageal, colorectal and head and neck cancer. Although several factors and disease states can promote significant loss of weight, it is important to highlight that the difference between cachexia and regular weight loss (as simply due to reduced food and calorie intake) is that it happens involuntarily, likely also because of metabolic, hormonal and inflammatory changes that cause the body to break down muscle mass uncontrollably. We and others have shown that the development of cachexia in patients with cancer will also increase the toxicity of anti-cancer treatments and reduce their tolerability, thus also negatively impacting patients’ survival. Although the causes of cachexia remain obscure, we now know that imbalances in the levels of several circulating factors (such as hormones, cytokines and growth factors) usually lead to weight loss and wasting of muscles, as well as to loss of bone mass, even in the absence of bone metastases. In particular, a partially unexplored aspect of cachexia represents the connection between loss of skeletal muscle mass and the occurrence of bone loss and osteoporosis, as often shown in patients affected with cancer or undergoing radio- or chemotherapy treatments. Observations from our group supports the idea that skeletal muscle wasting may also play a role in inducing cancer-associated bone loss, thus leading to the hypothesis that muscle and bone are regulated in tandem in cachexia. Aside from musculoskeletal complications, occurrence of cancers such as colorectal cancer also causes perturbations to the liver, especially in its most advanced/metastatic stages. We and others have recently demonstrated that colorectal cancer triggers oxidative-to-glycolytic shifts in hepatic metabolism, along with increased gluconeogenesis and net negative energy balance, which are hallmarks of cachexia. Our group is actively involved in understanding the musculoskeletal complications resulting from abnormal hepatokine secretion in colorectal cancer to the extent of identifying novel cachexia treatments.
Current projects:
Role or RANKL in ovarian cancer-induced musculoskeletal complications
Role of IGFBP1 in the liver-bone-muscle axis in colorectal cancer
Characterization of cachexia in in vivo models of head and neck cancer
Effects of pre-existing obesity in cancer-induced cachexia
Characterization of chemotherapy-induced cachexia
New mediators of pediatric cancer cachexia
Regulation of muscle regeneration in cancer
Identification of novel regulators of muscle and bone loss in aging
Publications:
Andrea Bonetto PhD
Associate Professor - Cancer Cachexia Research
- Pathology (SOM)
Areas of Expertise
cancer cachexia, muscle physiology, muscle pathology, cancer-associated musculoskeletal disease, sarcopenia of aging, IL-6, STAT3, RANKL, chemotherapy toxicities, ovarian cancer, colorectal cancer, tumor-host interactions, muscular dystrophy
Education, Licensure & Certifications
UNDERGRADUATE
University of Torino, Italy
MSc., Industrial Biotechnology
07/2004
GRADUATE
University of Torino, Italy
Ph.D., Experimental Pathology
11/2008
POSTDOCTORAL
University of Genova, Italy
Post-Doc, Neuromuscular diseases
01/2009 – 01/2010
University of Miami Miller School of Medicine, Miami, FL
Post-Doc, Cancer cachexia
03/2010 – 07/2011
Thomas Jefferson University, Philadelphia, PA
Post-Doc, Cancer cachexia
08/2011 – 07/2013
Awards
R21 CA190028-01 (NIH/NCI)
(PQB-3) Roles of skeletal muscle mass in chemotherapy-associated cachexia
09/2014 - 08/2016
V2017-021 (V Foundation Scholar Grant)
Mechanisms and treatment of chemotherapy-induced cachexia and muscle weakness
11/2017 - 10/2019
Research Scholar
Showalter Research Trust
07/2018
Excellence in Research
4th Cancer Cachexia Conference
09/2018
132013-RSG-18-010-01-CCG (American Cancer Society)
Mechanisms of chemotherapy-induced muscle weakness and fatigue
07/2018 - 06/2022
R01 AR079379 (NIH/NIAMS)
Targeting RANKL for the treatment of muscle and bone defects in cachexia
07/2021 - 06/2026
R01 AR080051 (NIH/NIAMS)
IGFBP1 mediates a liver-bone-muscle axis in colorectal cancer cachexia
08/2022 – 07/2027
Affiliations
-Department of Pathology, University of Colorado Anschutz Medical Campus
-University of Colorado Comprehensive Cancer Center