Regulation of Hypoxia Dependent Reprogramming of Cancer Metabolism - Role of HIF-1 and Its Potential Therapeutic Implications in Leukemia

Sep 21, 2026

Uploaded by Hazel

Metabolic reprogramming supports cancer cells’ high energy demand and is essential for the survival of malignancies. Cancer cells show altered metabolism compared with non-malignant cells, driven by pathways such as mTOR, Akt, PI3K, and hypoxia-inducible factor-1 (HIF-1). HIF-1 coordinates gene expression involved in metabolism, survival, invasion, proliferation, and angiogenesis. The article reviews metabolic alterations, key pathways, molecular mechanisms, and summarizes potential therapeutic targets, with special attention to hypoxia and leukemia. A concise overview of HIF-1α roles across common hematological malignancies is provided.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Abstract

Introduction

Warburg effect and hypoxia in tumors

Internal and external drivers of metabolic reprogramming

HIF-1-induced Metabolic Reprogramming in Hypoxia: Glucose metabolism

REVIEW Editorial Process: Submission:08/18/2023 Acceptance:04/20/2024 Regulation of Hypoxia Dependent Reprogramming of Cancer Metabolism: Role of HIF-1 and Its Potential Therapeutic Implications in Leukemia Sandeep Pandey1, Ranjana Singh1 *, Nimra Habib1, Ramesh Mani Tripathi1, Rashmi Kushwaha2, Abbas Ali Mahdi1 Abstract Metabolic reprogramming occurs to meet cancer cells’high energy demand. Its function is essential to the survival of malignancies. Comparing cancer cells to non-malignant cells has revealed that cancer cells have altered metabolism. Several pathways, particularly mTOR, Akt, PI3K, and HIF-1 (hypoxia-inducible factor-1) modulate the metabolism of cancer. Among other aspects of cancer biology, gene expression in metabolism, survival, invasion, proliferation, and angiogenesis of cells are controlled by HIF-1, a vital controller of cellular responsiveness to hypoxia. This article examines various cancer cell metabolisms, metabolic alterations that can take place in cancer cells, metabolic pathways, and molecular aspects of metabolic alteration in cancer cells placing special attention on the consequences of hypoxia-inducible factor and summarising some of their novel targets in the treatment of cancer including leukemia. A brief description of HIF-1α’s role and target in a few common types of hematological malignancies (leukemia) is also elucidated in the present article. Keywords: Metabolic Reprogramming-Cancer Cell Metabolism-Hypoxia-Inducible Factor-1 (HIF-1) Asian Pac J Cancer Prev, 25 (4), 1121-1134 Introduction Cancer cells require a higher rate of energy for their active proliferation and growth, due to which tumors become hypoxic and they need to rely on non-oxidative energy sources . The first observation of abnormal metabolism in cancer cells was identified by Otto Warburg and is called as Warburg effect. Hypoxia is considered a normal finding in tumors. Cancer cells adapt to hypoxia by using pathways of physiological adaptation that encourage a shift from oxidative to glycolytic metabolism. In healthy cells, energy homeostasis is maintained by different metabolic pathways like Glycolysis, Tricarboxylic acid cycle, and lipogenesis and these cells have a relatively low rate of cell division. These cells primarily use glucose asan energy source, which is entirely oxidized by glycolysis, TCA/Kreb cycle, and oxidative phosphorylation. Most non-proliferating cells depend on ATP production for their metabolic needs which are produced through oxidative phosphorylation. In cancer cells, a series of mutations impact multiple signaling and metabolic pathways leading to metabolic reprogramming. Both genetic mutations and tumor microenvironment are responsible for altering the metabolic pathways in cancer cells which leads to enhancement in cell growth and accelerates the rate of cell division. Both internal and external influences can affect cancer cells. Genetic mutations are among the inside contributors. A number of tumor suppressor genes and oncogenes regulate the metabolic reprogramming of cancer cells. Genes like HIFI, P13K-ATK/mTOR, MYC, KRAS, and P53 are responsible for altering signaling in metabolic pathways in cancer cells. MYC, Phosphatidylinositol 3-kinase, and HIFs have been observed in increasing glycolytic activity. Oncogenes like Ras and Src are thought to promote glycolysis by activating glucose transporter 1. P53 is one of the most important tumor suppressor proteins which is responsible for blocking the glycolytic pathway. Activation of the P13 kinase/ serine/threonine kinase AKT pathway is responsible for enhanced glucose uptake and glycolysis. Cancer cells are influenced by external stimuli like the tumor microenvironment. The hypoxia, PH, and nutrient content in the tumor microenvironment have an effect on the metabolism of cancer cells. Both these internal and external factors lead to abnormal metabolism in cancer cells. Metabolic adaptations include Increased ATP produc

FAQs

How does hypoxia contribute to metabolic reprogramming in cancer cells?

Tumors become hypoxic, and cancer cells adapt by shifting from oxidative to glycolytic metabolism. This adaptation changes energy utilization to better support proliferation and survival.

Which signaling pathways and factors regulate cancer metabolism according to the article?

The article highlights mTOR, Akt, PI3K, and especially HIF-1 as regulators of cancer metabolic control. It links HIF-1 to gene expression programs governing metabolism and tumor-related functions.

What is the role of HIF-1 in cancer cell biology beyond metabolism?

HIF-1 controls cellular responsiveness to hypoxia and regulates gene expression tied to survival, invasion, proliferation, and angiogenesis. The article emphasizes HIF-1’s importance for multiple cancer phenotypes.

Sep 21, 2026

Uploaded by Hazel