Multilayer-omics analysis of cancer cachexia: integrative approach to identify biomarkers and drug targets

Abstract

Cancer cachexia is a syndrome characterized by the severe wasting of skeletal muscle tissue; that is estimated to affect more than 50% of all cancer patients and results in lower quality of life due to compromised fatigue, weakness, immune function, insulin resistance and poor tolerance and response to chemotherapy. Remarkably, approximately 30% of cancer-related deaths are estimated as a result of cachexia. There is no effective targeted therapy for muscle wasting in cancer cachexia. The complexity of mechanisms controlling gene expression in this process suggests the involvement of additional regulatory molecular interactions, in this way Omic studies have helped clarify the impact of regulatory elements on disease. The feasibility of genome-wide analysis of Omics marks at nucleotide resolution using Next Generation Sequencing has already been demonstrated in the ENCODE projects, as well as the TCGA consortium. Considering this, our hypothesis is that comparison of muscles omics profiles from healthy and cancer cachexia will reveal disease novel specific signatures and a better understanding of the cellular signaling mechanisms and gene regulation in muscle, which will lead to the identification of candidate genes, involved in the pathogenesis, and may be helpful in finding biomarkers and drug targets. (AU)