Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma - Systemic and Locoregional Options

Sep 24, 2026

Hepatocellular cancer (HCC) is the most common primary liver cancer and a leading cause of cancer-related death. For unresectable disease, locoregional treatments such as TAE, TACE, and radioembolization improve survival, yet ischemia and hypoxia can be resisted through metabolic reprogramming. Tumors survive embolization by adopting the Warburg effect, shifting to aerobic glycolysis even in oxygenated conditions. This review summarizes HCC hypoxia adaptation mechanisms and evaluates anti-glycolytic therapies, including systemic and locoregional options.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Introduction

Locoregional therapies and limitations

Hypoxia adaptation and the Warburg effect

Warburg Effect

Review Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma: Systemic and Locoregional Options Miles Pourbaghi 1, Leila Haghani 1, Ken Zhao 1, Anita Karimi 1, Brett Marinelli 1, Joseph P. Erinjeri 1, Jean-Francois H. Geschwind 2 and Hooman Yarmohammadi 1, * Citation: Pourbaghi, M.; Haghani, L.; Zhao, K.; Karimi, A.; Marinelli, B.; Erinjeri, J.P.; Geschwind, J.-F.H.; Yarmohammadi, H. Anti-Glycolytic Drugs in the Treatment of Hepatocellular Carcinoma: Systemic and Locoregional Options. Curr. Oncol. 2023, 30, 6609–6622. [https://](https://)[ ](https://)[doi.org/10.3390/curroncol30070485](doi.org/10.3390/curroncol30070485) Received: 5 June 2023 Revised: 1 July 2023 Accepted: 4 July 2023 Published: 10 July 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Department of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; [pourbam@mskcc.org](pourbam@mskcc.org) (M.P.); [zhaok@mskcc.org](zhaok@mskcc.org) (K.Z.); [karimia@mskcc.org](karimia@mskcc.org) (A.K.); [marinelb@mskcc.org](marinelb@mskcc.org) (B.M.); [erinjerj@mskcc.org](erinjerj@mskcc.org) (J.P.E.) 2 Oncology and Image-Guided Therapy, NAMSA, New York, NY 10021, USA;[jfgeschwind@gmail.com](jfgeschwind@gmail.com) * [Correspondence: yarmohah@mskcc.org](Correspondence: yarmohah@mskcc.org); Tel.: +1-212-636-2234; Fax: +1-212-717-3325 Abstract: Hepatocellular cancer (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death. Locoregional therapies, including transarterial embolization (TAE: bland embolization), chemoembolization (TACE), and radioembolization, have demonstrated survival beneﬁts when treating patients with unresectable HCC. TAE and TACE occlude the tumor's arterial supply, causing hypoxia and nutritional deprivation and ultimately resulting in tumor necrosis. Embolization blocks the aerobic metabolic pathway. However, tumors, including HCC, use the “Warburg effect” and survive hypoxia from embolization. An adaptation to hypoxia through the Warburg effect, which was ﬁrst described in 1956, is when the cancer cells switch to glycolysis even in the presence of oxygen. Hence, this is also known as aerobic glycolysis. In this article, the adaptation mechanisms of HCC, including glycolysis, are discussed, and anti-glycolytic treatments, including systemic and locoregional options that have been previously reported or have the potential to be utilized in the treatment of HCC, are reviewed. Keywords: hepatic artery embolization; hepatocellular carcinoma; Warburg effect; glycolysis; antiglycolytic drugs 1. Introduction Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is the third leading cause of cancer-related death [1] . (Liver transplant, surgical resection, and ablation are among the curative treatment options [2] . However, most patients are not candidates for curative options at the time of their diagnosis. These patients are treated with other options, including locoregional therapy, i.e., trans-arterial embolization (TAE or bland embolization), transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and hepatic artery infusion (HAI) . TAE and TACE can achieve local tumor growth control and improve overall survival (OS) in patients with unresectable HCC [3] . HCC is a hypervascular tumor that relies predominately (85%) on the hepatic artery. By contrast, the liver parenchyma relies primarily (75%) on the portal vein. TAE and TACE occlude the hepatic artery with embolic material causing ischemia and depriving the tumor of essential nutrients. Despite the high success rate reported with TAE and

FAQs

Why are locoregional therapies used for unresectable HCC?

Transarterial embolization and related approaches can improve survival by controlling local tumor growth. They work by blocking arterial supply, but recurrence and limited overall survival remain concerns.

What role does hypoxia play after TAE/TACE?

Hypoxia can inhibit oxidative phosphorylation and contribute to tumor necrosis. However, tumor evaluations show that many lesions do not achieve complete necrosis, indicating adaptation to hypoxia.

How does the Warburg effect enable HCC to survive embolization?

HCC can convert to a high glycolytic state even when oxygen is present, described as aerobic glycolysis. This metabolic switch allows cancer cells to maintain energy production and proliferation despite hypoxia.

Sep 24, 2026

Uploaded by Taylor Morgan