Related Experiment Video

Updated: Feb 9, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

11.2K

Cancer Lipid Metabolism Confers Antiangiogenic Drug Resistance

Hideki Iwamoto1, Mitsuhiko Abe1, Yunlong Yang2

  • 1Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 171 77, Sweden; Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.

Cell Metabolism
|June 5, 2018
PubMed

Insights

Tumor cells develop resistance to antiangiogenic drugs (AAD) by reprogramming lipid metabolism. Inhibiting fatty acid oxidation enhances AAD efficacy, offering a new therapeutic strategy.

Area of Science:

  • Oncology
  • Cancer Metabolism
  • Molecular Biology

Background:

  • Intrinsic and evasive resistance to antiangiogenic drugs (AAD) is a significant challenge in cancer therapy.
  • The underlying molecular mechanisms of AAD resistance are not fully understood.

Purpose of the Study:

  • To investigate AAD-triggered, lipid-dependent metabolic reprogramming as a novel mechanism of AAD resistance.
  • To explore the therapeutic potential of targeting lipid metabolism in combination with AAD.

Main Methods:

  • Analysis of tumor angiogenesis in adipose and non-adipose environments under AAD treatment.
  • Investigation of metabolic reprogramming, including fatty acid oxidation and free fatty acid (FFA) uptake, in AAD-treated tumors.
  • Assessment of the role of carnitine palmitoyl transferase 1A (CPT1) in AAD resistance using genetic and pharmacological inhibition.

Main Results:

  • AAD treatment triggers lipid metabolism reprogramming, characterized by increased fatty acid oxidation and FFA uptake, promoting cancer cell proliferation.
  • Tumor angiogenesis is sensitive to AAD in both adipose and non-adipose tissues, but AAD-treated tumors in adipose tissue exhibit accelerated growth with minimal vasculature.
  • Inhibition of CPT1 significantly impairs FFA-induced proliferation and enhances the anti-tumor effects of AAD.

Conclusions:

  • Lipid metabolism reprogramming is a key mechanism of AAD resistance.
  • Combining antiangiogenic therapy with agents that inhibit lipid metabolism, specifically CPT1, represents a promising strategy to overcome AAD resistance and improve anti-tumor efficacy.
Keywords:
VEGFangiogenesisantiangiogenic therapycancerdrug resistancehypoxialipid metabolismmetastasistumor microenvironmentβ-oxidation

More Related Videos

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

14.4K
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance08:45

Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance

Published on: December 28, 2017

14.2K

Related Concept Videos

Overview of Lipid Metabolism01:24

Overview of Lipid Metabolism

Lipid metabolism is a crucial process in the human body that involves the synthesis and degradation of lipids. This process is essential for energy production, cell membrane formation, and hormone production, among other functions.
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
5.5K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
Drug Metabolism: Phase I Reactions01:17

Drug Metabolism: Phase I Reactions

A phase I reaction is a biochemical process that introduces a functionally reactive polar group to a substance. This transformation predominantly occurs in the liver, facilitated by the cytochrome P450 system of hemoproteins situated in the lipophilic endoplasmic reticulum of cells. The metabolite generated through this process can have varying polarities. If it is sufficiently polar, it can be easily excreted in the urine due to its water compatibility. However, if the metabolite is nonpolar,...
5.0K
Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
5.2K
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses...
242
What is Metabolism?00:52

What is Metabolism?

Overview
132.1K