4.7 Review

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

Journal

FRONTIERS IN PHARMACOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.991052

Keywords

tumor microenvironment; hepatocellular carcinoma; sorafenib resistance; tumor-associated immune-suppressive cells; immunosuppressive factors; hypoxia

Funding

  1. National Natural Science Foundation of China
  2. National Natural Science Foundation of Shandong Province
  3. Young Taishan Scholars Program of Shandong Province
  4. [81873249]
  5. [82074360]
  6. [ZR2019MH058]
  7. [tsqn201909200]

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The "Translation" section introduces the limitations of sorafenib treatment for hepatocellular carcinoma, including drug resistance. It mentions the important roles of tumor microenvironment and immune escape in tumor occurrence and resistance to anti-cancer drugs, highlighting the importance of overcoming sorafenib resistance in liver cancer.
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.

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