Link of sorafenib resistance with the tumor microenvironment in hepatocellular carcinoma: Mechanistic insights

Abstract

Sorafenib, a multi-kinase inhibitor with antiangiogenic, antiproliferative, and proapoptotic properties, is the first-line treatment for patients with late-stage hepatocellular carcinoma (HCC). However, the therapeutic effect remains limited due to sorafenib resistance. Only about 30% of HCC patients respond well to the treatment, and the resistance almost inevitably happens within 6 months. Thus, it is critical to elucidate the underlying mechanisms and identify effective approaches to improve the therapeutic outcome. According to recent studies, tumor microenvironment (TME) and immune escape play critical roles in tumor occurrence, metastasis and anti-cancer drug resistance. The relevant mechanisms were focusing on hypoxia, tumor-associated immune-suppressive cells, and immunosuppressive molecules. In this review, we focus on sorafenib resistance and its relationship with liver cancer immune microenvironment, highlighting the importance of breaking sorafenib resistance in HCC.

Ropivacaine combined with sorafenib attenuates hepatocellular carcinoma cell proliferation and metastasis by inhibiting the miR‐224/HOXD10 axis

“…21 However, newer therapies based primarily on Sor appear to induce a modest increase in HCC patient survival. 22 However, significant drug resistance to Sor reduces the therapeutic effect of patients. 23 At the same time, over 50% of patients experience severe clinical side effects.…”

“…Only patients who cannot be treated by resection are candidates for drug therapy 21 . However, newer therapies based primarily on Sor appear to induce a modest increase in HCC patient survival 22 . However, significant drug resistance to Sor reduces the therapeutic effect of patients 23 .…”

The effects of low-dose sorafenib on epithelial-mesenchymal transition and multidrug resistance markers in HepG2 cell line

“…Similarly, several studies reported that sorafenib inhibits EMT in a variety of experimental settings [21][22][23]. Moreover, sorafenib resistance is often associated with changes in the tumor microenvironment, and sorafenib-resistant cells were shown to exhibit EMT [24][25][26].…”

Role of exosomes in hepatocellular carcinoma and the regulation of traditional Chinese medicine

“…Astragaloside IV, a major effective component of Astragalus membranaceus, increases the secretion of exosomal miR-126-3p and miR-126-5p from human endothelial progenitor cells and promotes angiogenesis ( Xiong et al, 2020 ). Tanshinone IIA, the main pharmacological component of Radix Salvia miltiorrhiza, protects against chronic obstructive pulmonary disease via exosome-shuttled miR-486-5p ( Tian X et al, 2022 ).…”