Evidence map›Paper›PMID 33795234›Full record

ReviewCancer discovery2021

Synthetic Lethality in Cancer Therapeutics: The Next Generation.

Jeremy Setton, Michael Zinda, Nadeem Riaz, Daniel Durocher, Michal Zimmermann, Maria Koehler, Jorge S Reis-Filho, Simon N Powell

Abstract readReview
In one paragraph

Review in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

125 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Genomic and Epigenomic ctDNA Profiling in Liquid Biopsies from Heavily Pretreated Patients with DNA Damage Response-Deficient Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
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65 more citing papers are in PubMed but not listed here.

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

8 authors.

Jeremy SettonMemorial Sloan Kettering Cancer Center, New York, New York.
Michael ZindaRepare Therapeutics, Cambridge, Massachusetts.
Nadeem RiazMemorial Sloan Kettering Cancer Center, New York, New York.
Daniel DurocherLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.ORCID 0000-0003-3863-8635
Michal ZimmermannRepare Therapeutics, St-Laurent, Quebec, Canada.
Maria KoehlerRepare Therapeutics, Cambridge, Massachusetts.
Jorge S Reis-FilhoMemorial Sloan Kettering Cancer Center, New York, New York.
Simon N PowellMemorial Sloan Kettering Cancer Center, New York, New York. powells@mskcc.org.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Targeting Polθ to Overcome PARP Inhibitor Resistance in Homologous Recombination Deficient Breast CancerP50CA247749 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI Simon N. Powell · 2020 to 2026
$16.3M
NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA247749
6 · The paper itself

Abstract

Synthetic lethality (SL) provides a conceptual framework for tackling targets that are not classically "druggable," including loss-of-function mutations in tumor suppressor genes required for carcinogenesis. Recent technological advances have led to an inflection point in our understanding of genetic interaction networks and ability to identify a wide array of novel SL drug targets. Here, we review concepts and lessons emerging from first-generation trials aimed at testing SL drugs, discuss how the nature of the targeted lesion can influence therapeutic outcomes, and highlight the need to develop clinical biomarkers distinct from those based on the paradigms developed to target activated oncogenes. SIGNIFICANCE: SL offers an approach for the targeting of loss of function of tumor suppressor and DNA repair genes, as well as of amplification and/or overexpression of genes that cannot be targeted directly. A next generation of tumor-specific alterations targetable through SL has emerged from high-throughput CRISPR technology, heralding not only new opportunities for drug development, but also important challenges in the development of optimal predictive biomarkers.

Indexed as

Synthetic Lethal MutationsDrug DevelopmentGenes, Tumor SuppressorHumansMolecular Targeted TherapyNeoplasms

Identifiers

PMID33795234
PMCPMC8295179

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.