Related Experiment Video
Updated: Jun 7, 2026
Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
Published on: December 26, 2016
Sugar-free approaches to cancer cell killing
N El Mjiyad1, A Caro-Maldonado, S Ramírez-Peinado
1Cell Death Regulation Group, IDIBELL (Bellvitge Biomedical Research Institute), L'Hospitalet de Llobregat, Barcelona, Spain.
Abstract:
Tumors show an increased rate of glucose uptake and utilization. For this reason, glucose analogs are used to visualize tumors by the positron emission tomography technique, and inhibitors of glycolytic metabolism are being tested in clinical trials. Upregulation of glycolysis confers several advantages to tumor cells: it promotes tumor growth and has also been shown to interfere with cell death at multiple levels. Enforcement of glycolysis inhibits apoptosis induced by cytokine deprivation. Conversely, antiglycolytic agents enhance cell death induced by radio- and chemotherapy. Synergistic effects are likely due to regulation of the apoptotic machinery, as glucose regulates activation and levels of proapoptotic BH3-only proteins such as Bim, Bad, Puma and Noxa, as well as the antiapoptotic Bcl-2 family of proteins. Moreover, inhibition of glucose metabolism sensitizes cells to death ligands. Glucose deprivation and antiglycolytic drugs induce tumor cell death, which can proceed through necrosis or through mitochondrial or caspase-8-mediated apoptosis. We will discuss how oncogenic pathways involved in metabolic stress signaling, such as p53, AMPK (adenosine monophosphate-activated protein kinase) and Akt/mTOR (mammalian target of rapamycin), influence sensitivity to inhibition of glucose metabolism. Finally, we will analyze the rationale for the use of antiglycolytic inhibitors in the clinic, either as single agents or as a part of combination therapies.
Insights
Tumors rely heavily on glucose. Inhibiting this sugar metabolism can trigger cancer cell death and enhance the effectiveness of cancer treatments like radiation and chemotherapy.
Area of Science:
- Biochemistry
- Oncology
- Cell Biology
Background:
- Tumors exhibit elevated glucose uptake and utilization, a hallmark exploited for imaging and therapeutic strategies.
- Glycolysis upregulation provides survival advantages to cancer cells, promoting growth and inhibiting apoptosis.
- Glucose metabolism is intricately linked to cell death pathways, influencing sensitivity to various stimuli.
Purpose of the Study:
- To explore the role of glycolysis in tumor growth and survival.
- To investigate how inhibiting glucose metabolism affects cancer cell death.
- To analyze the influence of oncogenic signaling pathways on sensitivity to antiglycolytic agents.
Main Methods:
- Review of existing literature on glucose metabolism in cancer.
- Analysis of the effects of antiglycolytic agents on apoptosis and cell death.
- Discussion of oncogenic pathways (p53, AMPK, Akt/mTOR) in metabolic stress signaling.
Main Results:
- Inhibition of glycolysis can sensitize tumor cells to apoptosis and death ligands.
- Antiglycolytic agents enhance the efficacy of radio- and chemotherapy, suggesting synergistic effects.
- Glucose metabolism influences the balance of proapoptotic and antiapoptotic proteins within the Bcl-2 family.
Conclusions:
- Targeting glucose metabolism is a promising therapeutic strategy in oncology.
- Antiglycolytic inhibitors can be used as single agents or in combination therapies for cancer treatment.
- Understanding the interplay between oncogenic pathways and glucose metabolism is crucial for optimizing cancer therapy.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against specific...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...