Resistance a major hindrance to chemotherapy in hepatocellular carcinoma: an insight

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality, accounting for almost 90% of total liver cancer burden. Surgical resection followed by adjuvant and systemic chemotherapy are the most meticulously followed treatment procedures but the complex etiology and high metastatic potential of the disease renders surgical treatment futile in majority of the cases. Another hindrance to the scenario is the acquired resistance to drugs resulting in relapse of the disease. Hence, to provide insights into development of novel therapeutic targets and diagnostic biomarkers, this review focuses on the various molecular mechanisms underlying chemoresistance in HCC. We have provided a comprehensive summary of the various strategies adopted by HCC cells, extending from apoptosis evasion, autophagy activation, drug expulsion to epigenetic transformation as modes of therapy resistance. The role of stem cells in imparting chemoresistance is also discussed. Furthermore, the review also focuses on how this knowledge might be exploited for the development of an effective, prospective therapy against HCC.

Keywords: Apoptosis; Autophagy; Cancer; Chemoresistance; HCC; Metastasis.

Fig. 1

The critical cellular and non-cellular components of HCC tumor microenvironment

Fig. 2

Potential molecular mechanisms that regulate chemoresistance in Hepatocellular Carcinoma