My research on the physiology and pathology of cancer-associated wasting of skeletal muscle spans more than 30 years. Key invited reviews and commentary (i.e. Annual Rev Med 2010, Nature Reviews Clin Oncol 2013; 10(2):90-9; J Clinical Oncol 2013; 31(10):1257-8) outline my understanding of the pathophysiology of cachexia and muscle wasting. I was the senior author of the international consensus framework for definition of cancer cachexia (Lancet Oncology 2011; 12:489-95).
I have made numerous contributions to the understanding of the mechanisms of cancer-associated cachexia and muscle wasting using standardized animal models. One area of research is the role of cytokines on protein metabolism in skeletal muscle (Baracos, VE et al. 1983, New England J. Med. 508:553-558). Inflammation-dependant muscle wasting (i.e. Mackenzie ML et al. Am J Physiol 2005, 289:E 527-E533; Braun T et al. 2011 J Exptl. Med.208:2449-63) is an important link in the central and peripheral control of muscle wasting in infection, cancer and injury. The role of specific degradative system(s) in different instances of muscle wasting included the identification of a cytokine-induced catabolic pathway (Kwak et al. 2004; Cancer Res. 64:8193-8). A potential therapy, selumetinib, is a MEK kinase inhibitor causing strong systemic suppression of interleukin 6 in patients with cholangiocarcinoma, and this agent caused a rapid muscle anabolism in 80% of treated individuals (Prado et al. Br J Cancer 2012 106(10):1583-6)
My clinical research is focused on the underlying causes of muscle wasting in cancer patients: the role of tumor progression (Lieffers JR, et al. Am J Clin Nutr. 2009; 89:1173-9), of specific drugs used in cancer therapy such as sorafenib (Antoun S et al. J Clin Oncol, 2010; 28:1054-60) and of a putative muscle proteolysis-inducing factor (Wieland BM et al Clin Cancer Res. 2007; 13: 4984-92). A significant zone of current research activity concerns measurement of cancer-related muscle wasting using computed tomography. We established crucial capacity to exploit CT images taken for cancer diagnosis and follow-up, to extract data on skeletal muscle loss. Severe muscle depletion (sarcopenia) is independently prognostic for overall survival (Prado CM et al. Lancet Oncol. 2008; 9:629-35; Martin et al. J Clin Oncol 2013, 31(12):1539-47). Furthermore, sarcopenic cancer patients are susceptible to excess toxicity during chemotherapy treatment (Prado CM et al Clin Cancer Res. 2007; 13(11):3264-8 and 2009:15:2920-6), necessitating dose reductions or treatment delays that ultimately may reduce the efficacy of their treatment.
I am PI of a major organized effort to develop clinical cachexia research (Cachexia-Network) to provide synergy in (i) knowledge generation (ii) knowledge synthesis across the larger body of research findings, (iii) dissemination of findings to specific target groups, (iv) engagement strategies to relevant clinical practice communities and scientific communities and (v) training a new cadre of researchers.
body composition, cancer, nutrition