Page 68 - GPD-3-2

Gene & Protein in Disease

REVIEW ARTICLE
Opportunities and challenges of integrating

HIF-1 into clinical practice for cancer treatment

3
2
1
Maria Vasileiou * , Christina Tsianava , Sotirios Charalampos Diamantoudis ,
4
Teodora Mazneva , and Kleio Giortsiou 3
1 Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of
Athens, Athens, Greece
2 Department of Pharmacy, School of Health Sciences, University of Patras, Rion, Greece
3 School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, Thessaloniki,
Greece
4 Faculty of Pharmacy, Ss Cyril and Methodius University, Skopje, Republic of North Macedonia

Abstract

The Warburg effect is one of the most studied mechanisms involved in cancer
progression. It refers to the increased glucose uptake by cancer cells through aerobic
glycolysis, instead of the Krebs cycle that takes place under normal conditions, followed
by lactic acid fermentation. This mechanism is regulated by hypoxia-inducible factor-1
(HIF-1), a transcription factor that regulates the expression of genes responsible for
the synthesis of proteins involved in glucose metabolism. Overexpression of HIF-1
has been linked to the Warburg effect. While several HIF-1-targeted strategies have
been investigated, the majority have proven to be unsuccessful, especially in cases
*Corresponding author: of aggressive tumors with hypoxic tumor microenvironments. Current strategies
Maria Vasileiou expand beyond conventional chemotherapeutic agents and include chemodynamic
(mariavasileiou65@gmail.com) therapy, radiation therapy, and immune checkpoint molecules. The aim of this
Citation: Vasileiou M, Tsianava literature review is to highlight the implication of HIF-1 in the Warburg effect and the
C, Diamantoudis SC, Mazneva limitations that render cancer treatment less effective.
T, Giortsiou K. Opportunities and
challenges of integrating HIF-1
into clinical practice for cancer Keywords: HIF-1; Warburg effect; Cancer metabolism; Hypoxia; Angiogenesis; Drug
treatment. Gene Protein Dis.
2024;3(2):3431. resistance
doi: 10.36922/gpd.3431
Received: April 16, 2024
Accepted: June 18, 2024 1. Introduction
Published Online: June 28, 2024 1.1. Overview of Warburg effect
Copyright: © 2024 Author(s).
This is an Open-Access article Malignancies pose a major public health threat, being ranked as the most burdensome
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distributed under the terms of the condition as measured in disability-adjusted life years. According to the American
Creative Commons Attribution Cancer Society, the most prominent cancers in each gender are prostate cancer and breast
License, permitting distribution,
and reproduction in any medium, cancer, with 268,490 and 287,850 cases, respectively. Lung cancer is also prevalent in both
provided the original work is males and females, claiming the lives of 130,180 Americans and accounting for 18.85%
properly cited. of the total 690,360 cancer-related deaths. According to the World Health Organization
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Publisher’s Note: AccScience (WHO), the most prevalent cancer type in 2020 was breast cancer, followed by lung,
Publishing remains neutral with colon, and rectal cancers. The cancers with the highest mortality rates were lung, colon,
regard to jurisdictional claims in 3
published maps and institutional rectum cancer, and hepatocellular carcinoma. Future projections indicate that, under
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affiliations. current trends, cancer will remain a significant threat in the upcoming years. According

Volume 3 Issue 2 (2024) 1 doi: 10.36922/gpd.3431