Evidence map›Paper›PMID 35264777›Full record

ReviewNature reviews. Cancer2022

Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.

Marilyne Labrie, Joan S Brugge, Gordon B Mills, Ioannis K Zervantonakis

Open access · greenAbstract readReview
In one paragraph

Review in Nature reviews. Cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers.

0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed
27.3field-weighted citation impact, top 1% 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

198 citing papers in PubMed, 334 citations in OpenAlex.

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  8. Overcoming Drug Resistance by Paclitaxel Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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138 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

4 authors at 4 institutions in 3 countries.

Marilyne LabrieDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0003-3957-5533
Joan S BruggeDepartment of Cell Biology, Harvard Medical School, Boston, MA, USA.
Gordon B MillsDivision of Oncological Sciences, Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.ORCID http://orcid.org/0000-0002-0144-9614
Ioannis K ZervantonakisUPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. ioz1@pitt.edu.ORCID http://orcid.org/0000-0003-2386-9553
Harvard University · USOregon Health & Science University · USUniversité de Sherbrooke · CAUniversity of Pittsburgh · US

Funding

Project 2: Combined personal neoantigen-targeting cancer vaccines with immune checkpoint blockade for ovarian cancerP50CA240243 · NCI · DANA-FARBER CANCER INST · PI CASTRO, CESAR M · 2020 to 2024
$11.5M
Integrative bioinformatics and functional characterization of oncogenic driver aberrations in cancerU01CA217842 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DENEEN, BENJAMIN, MILLS, GORDON B. · 2017 to 2021
$3.6M
Mechanistic maps of adaptive responses to therapeutic stress to optimize combination therapies.U01CA253472 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI KORKUT, ANIL, LIANG, HAN · 2021 to 2025
$2.6M
Analysis of tumor-stroma signaling that mediates HER2-therapy resistance in breast cancerR00CA222554 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ZERVANTONAKIS, IOANNIS · 2019 to 2021
$741k
NCI NIH HHS P50 CA240243NCI NIH HHS R00 CA222554NCI NIH HHS U01 CA217842NCI NIH HHS U01 CA253472
6 · The paper itself

Abstract

Normal cells explore multiple states to survive stresses encountered during development and self-renewal as well as environmental stresses such as starvation, DNA damage, toxins or infection. Cancer cells co-opt normal stress mitigation pathways to survive stresses that accompany tumour initiation, progression, metastasis and immune evasion. Cancer therapies accentuate cancer cell stresses and invoke rapid non-genomic stress mitigation processes that maintain cell viability and thus represent key targetable resistance mechanisms. In this Review, we describe mechanisms by which tumour ecosystems, including cancer cells, immune cells and stroma, adapt to therapeutic stresses and describe three different approaches to exploit stress mitigation processes: (1) interdict stress mitigation to induce cell death; (2) increase stress to induce cellular catastrophe; and (3) exploit emergent vulnerabilities in cancer cells and cells of the tumour microenvironment. We review challenges associated with tumour heterogeneity, prioritizing actionable adaptive responses for optimal therapeutic outcomes, and development of an integrative framework to identify and target vulnerabilities that arise from adaptive responses and engagement of stress mitigation pathways. Finally, we discuss the need to monitor adaptive responses across multiple scales and translation of combination therapies designed to take advantage of adaptive responses and stress mitigation pathways to the clinic.

Indexed as

EcosystemNeoplasmsDNA DamageHumansImmunotherapyTumor Microenvironment

Identifiers

PMID35264777
PMCPMC9149051
OpenAlexW4220776360

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.