Evidence map›Paper›PMID 35723497›Full record

ReviewMolecular carcinogenesis2022

Targeting mitochondrial metabolism for metastatic cancer therapy.

Antonino Passaniti, Myoung Sook Kim, Brian M Polster, Paul Shapiro

Open access · greenAbstract readReview
In one paragraph

Review in Molecular carcinogenesis, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 47 citations in OpenAlex.

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  11. Resveratrol targets mitochondrial USP36-SOD2 to induce autophagy-ferroptosis and inhibit gastric cancer progression.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Antonino PassanitiThe Veteran's Health Administration Research & Development Service (VAMHCS), VA Maryland Health Care System (VAMHCS), Baltimore VA Medical Center, Baltimore, Maryland, USA.
Myoung Sook KimDepartment of Pathology and Department of Biochemistry & Molecular Biology, The Program in Molecular Medicine and the Marlene & Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Brian M PolsterDepartment of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Paul ShapiroDepartment of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, Maryland, USA.
University of Maryland, Baltimore · USUniversity of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer CenterVeterans Health Administration · US

Funding

Substrate specific ERK docking domain inhibitorsR01CA120215 · NCI · UNIVERSITY OF MARYLAND BALTIMORE · PI SHAPIRO, PAUL S · 2006 to 2010
$1.2M
Mitochondrial metabolism as a target of breast cancer therapyI01BX004904 · VA · BALTIMORE VA MEDICAL CENTER · PI PASSANITI, ANTONINO · 2020 to 2024
–
BLRD VA I01 BX004904NCI NIH HHS R01 CA120215
6 · The paper itself

Abstract

Primary tumors evolve metabolic mechanisms favoring glycolysis for adenosine triphosphate (ATP) generation and antioxidant defenses. In contrast, metastatic cells frequently depend on mitochondrial respiration and oxidative phosphorylation (OxPhos). This reliance of metastatic cells on OxPhos can be exploited using drugs that target mitochondrial metabolism. Therefore, therapeutic agents that act via diverse mechanisms, including the activation of signaling pathways that promote the production of reactive oxygen species (ROS) and/or a reduction in antioxidant defenses may elevate oxidative stress and inhibit tumor cell survival. In this review, we will provide (1) a mechanistic analysis of function-selective extracellular signal-regulated kinase-1/2 (ERK1/2) inhibitors that inhibit cancer cells through enhanced ROS, (2) a review of the role of mitochondrial ATP synthase in redox regulation and drug resistance, (3) a rationale for inhibiting ERK signaling and mitochondrial OxPhos toward the therapeutic goal of reducing tumor metastasis and treatment resistance. Recent reports from our laboratories using metastatic melanoma and breast cancer models have shown the preclinical efficacy of novel and rationally designed therapeutic agents that target ERK1/2 signaling and mitochondrial ATP synthase, which modulate ROS events that may prevent or treat metastatic cancer. These findings and those of others suggest that targeting a tumor's metabolic requirements and vulnerabilities may inhibit metastatic pathways and tumor growth. Approaches that exploit the ability of therapeutic agents to alter oxidative balance in tumor cells may be selective for cancer cells and may ultimately have an impact on clinical efficacy and safety. Elucidating the translational potential of metabolic targeting could lead to the discovery of new approaches for treatment of metastatic cancer.

Indexed as

Mitochondrial Proton-Translocating ATPasesNeoplasmsAdenosine TriphosphateAntioxidantsHumansMitochondriaOxidative PhosphorylationReactive Oxygen SpeciesAdenosine TriphosphateAntioxidantsMitochondrial Proton-Translocating ATPasesReactive Oxygen Speciescancer metastasisdrug mechanismskinase signalingmitochondriareactive oxygen speciestargeting OxPhos

Identifiers

PMID35723497
PMCPMC9378505
OpenAlexW4283169780

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.