Evidence map›Paper›PMID 28481306›Full record

ReviewCancers2017

MTH1 as a Chemotherapeutic Target: The Elephant in the Room.

Govindi J Samaranayake, Mai Huynh, Priyamvada Rai

Open access · goldAbstract readReview
In one paragraph

Review in Cancers, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.9field-weighted citation impact, top 5% 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

36 citing papers in PubMed, 68 citations in OpenAlex.

  1. Article
  2. Clinical Significance of NUDT1 (MTH1) Across Cancer Types.International journal of molecular sciences · 2025
    Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Chemical Tools for the Study of DNA Repair.Accounts of chemical research · 2022
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Inhibitors of DNA Glycosylases as Prospective Drugs.International journal of molecular sciences · 2020
    Review
  17. Review
  18. Article
  19. Article
  20. Article
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

3 authors at 2 institutions in 1 country.

Govindi J SamaranayakeDepartment of Medicine/Division of Hematology and Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. gjs26@med.miami.edu.
Mai HuynhDepartment of Medicine/Division of Hematology and Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. c.huynh@miami.edu.
Priyamvada RaiDepartment of Medicine/Division of Hematology and Oncology, University of Miami Miller School of Medicine, Miami, FL 33136, USA. prai@med.miami.edu.
University of Miami · USFlorida State University · US

Funding

MutT Homolog 1 as a Novel Mediator of RAS Oncogene-Induced Pro-Malignant PathwaysR01CA175086 · NCI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI RAI, PRIYAMVADA · 2013 to 2017
$1.6M
NCI NIH HHS R01 CA175086
6 · The paper itself

Abstract

Many tumors sustain elevated levels of reactive oxygen species (ROS), which drive oncogenic signaling. However, ROS can also trigger anti-tumor responses, such as cell death or senescence, through induction of oxidative stress and concomitant DNA damage. To circumvent the adverse consequences of elevated ROS levels, many tumors develop adaptive responses, such as enhanced redox-protective or oxidatively-generated damage repair pathways. Targeting these enhanced oxidative stress-protective mechanisms is likely to be both therapeutically effective and highly specific to cancer, as normal cells are less reliant on such mechanisms. In this review, we discuss one such stress-protective protein human MutT Homolog1 (MTH1), an enzyme that eliminates 8-oxo-7,8-dihydro-2'-deoxyguanosine triphosphate (8-oxodGTP) through its pyrophosphatase activity, and is found to be elevated in many cancers. Our studies, and subsequently those of others, identified MTH1 inhibition as an effective tumor-suppressive strategy. However, recent studies with the first wave of MTH1 inhibitors have produced conflicting results regarding their cytotoxicity in cancer cells and have led to questions regarding the validity of MTH1 as a chemotherapeutic target. To address the proverbial "elephant in the room" as to whether MTH1 is a bona fide chemotherapeutic target, we provide an overview of MTH1 function in the context of tumor biology, summarize the current literature on MTH1 inhibitors, and discuss the molecular contexts likely required for its efficacy as a therapeutic target.

Indexed as

cancerMTH1MTH1 inhibitorsnucleotide pooloxidative stressp53RAS oncogenetherapeutic target

Identifiers

PMID28481306
PMCPMC5447957
OpenAlexW2612974116

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.