Exploration of Combinational Therapeutic Strategies for HCC Based on TCGA HCC Database
Dong Yan, Chunxiao Li, Yantong Zhou, Yan Xue, Weihua Zhi, Haili Qian, Yue Han
Abstract
Hepatocellular carcinoma (HCC) is one of the most deadly types of cancer. Sorafenib is currently the only available first-line molecular targeted drug approved by the FDA for HCC. However, primary and secondary resistance is often encountered with treatment with sorafenib. Genomic alterations found in HCC represent potential targets to develop new drugs or new combinational strategies against this type of cancer. Here we analyzed genomic alterations from the TCGA database of HCC samples and the corresponding targeted drugs available to the clinic to identify candidate drugs that might hold promise when used in combination with sorafenib. Our results revealed that IL6, JAK1, LEPR and RAF1 related pathways were commonly altered in HCC, which have targeted drugs available in medical practice. Fourteen genes with available targeting drugs were frequently altered in HCC. The pathways and gene targets with the respective targeted drugs warrant further evaluation in clinical trials to determine their therapeutic value in the treatment of HCC, alone or in combination with sorafenib. In summary, the analysis of TCGA, identified a series of pathways with targeted drugs available that were altered in HCC. Combination treatment with specific targeted drugs, depending on the altered pathways found in individuals may provide a better treatment strategy that will ultimately improve individual patient survival.