4.7 Review

Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma

期刊

出版社

MDPI
DOI: 10.3390/ijms222313051

关键词

hepatocellular carcinoma; transarterial chemoembolization; drug delivery systems; tumour microenvironment; anthracyclines

资金

  1. Swedish Cancer Foundation (Cancerfonden) [20 1076PjF, 20 0175 F, CAN2018/602, CAN2021/603]
  2. Swedish Society for Medical Research (SSMF) [S17-0092]
  3. Swedish Research Council (Vetenskapsradet) [2018-03301, 2020-02367]
  4. Vinnova [2018-03301] Funding Source: Vinnova
  5. Swedish Research Council [2018-03301, 2020-02367] Funding Source: Swedish Research Council
  6. Formas [2020-02367] Funding Source: Formas

向作者/读者索取更多资源

Clinical data review highlights the limitations of transarterial chemoembolization (TACE) as a treatment for hepatocellular carcinoma (HCC) and the complex interactions between drug delivery, tumor targeting mechanisms, liver pathophysiology, patient and tumor heterogeneity, and resistance mechanisms. Understanding and addressing these factors are essential to improving the effectiveness of TACE and developing novel drug delivery systems for locoregional treatment of HCC.
Because diagnostic tools for discriminating between hepatocellular carcinoma (HCC) and advanced cirrhosis are poor, HCC is often detected in a stage where transarterial chemoembolization (TACE) is the best treatment option, even though it provides a poor survival gain. Despite having been used worldwide for several decades, TACE still has many limitations. First, there is a vast heterogeneity in the cellular composition and metabolism of HCCs as well as in the patient population, which renders it difficult to identify patients who would benefit from TACE. Often the delivered drug does not penetrate sufficiently selectively and deeply into the tumour and the drug delivery system is not releasing the drug at an optimal clinical rate. In addition, therapeutic effectiveness is limited by the crosstalk between the tumour cells and components of the cirrhotic tumour microenvironment. To improve this widely used treatment of one of our most common and deadly cancers, we need to better understand the complex interactions between drug delivery, local pharmacology, tumour targeting mechanisms, liver pathophysiology, patient and tumour heterogeneity, and resistance mechanisms. This review provides a novel and important overview of clinical data and discusses the role of the tumour microenvironment and lymphatic system in the cirrhotic liver, its potential response to TACE, and current and possible novel DDSs for locoregional treatment.

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