Evidence map›Paper›PMID 41115858›Full record

ArticleNature communications2025

Leveraging platinum-protein interactions to overcome chemoresistance.

Fang Wang, Jonathan Braverman, George Eng, Ozen Leylek, Nicholas L Petrone, Daniel S Honeycutt, Shinya Imada, Brian Pallares, Daiyao Zhang, Jason M Mrosla and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Improving Anticancer Activity of Doxorubicin by 4'-ACS medicinal chemistry letters · 2026
    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

17 authors.

Fang Wang *Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. fangwang@uri.edu.ORCID http://orcid.org/0000-0002-9192-6858
Jonathan Braverman *Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA. braverman@berkeley.edu.ORCID http://orcid.org/0000-0002-0759-7220
George EngDepartment of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ozen LeylekDepartment of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nicholas L PetroneDepartment of Chemistry, University of Rhode Island, Kingston, RI, USA.ORCID http://orcid.org/0009-0002-7494-359X
Daniel S HoneycuttDepartment of Chemistry, University of Rhode Island, Kingston, RI, USA.ORCID http://orcid.org/0000-0001-6143-4492
Shinya ImadaDepartment of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA.
Brian PallaresDepartment of Chemistry, Colgate University, Hamilton, NY, USA.ORCID http://orcid.org/0009-0003-8651-7392
Daiyao ZhangDepartment of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0009-0005-7259-0948
Jason M MroslaDepartment of Chemistry, Colgate University, Hamilton, NY, USA.ORCID http://orcid.org/0009-0001-1957-355X
Camellia S HuangDepartment of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0009-0008-0912-863X
Anna A GriadunovaInnovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
William K McCarthyDepartment of Chemistry, Colgate University, Hamilton, NY, USA.ORCID http://orcid.org/0009-0001-7778-0821
Jacob M GoldbergDepartment of Chemistry, Colgate University, Hamilton, NY, USA.ORCID http://orcid.org/0000-0002-8004-3769
Michael T HemannDepartment of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6776-2163
Stephen J LippardDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA. lippard@mit.edu.
Ömer H YilmazDepartment of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA, USA. ohyilmaz@mit.edu.ORCID http://orcid.org/0000-0002-7577-4612

Funding

Training CoreP20GM103430 · NIGMS · UNIVERSITY OF RHODE ISLAND · PI Ang Cai · 2012 to 2026
$63.6M
Understanding and Improving Platinum Anticancer DrugsR01CA034992 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI YILMAZ, OMER · 1985 to 2018
$6.8M
CHEMISTRY AND BIOLOGY OF PLATINUM ANTICANCER DRUGSR37CA034992 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LIPPARD, STEPHEN J. · 1990 to 2008
$5.7M
Developing high-throughput genetic perturbation strategies for single cells in cancer organoidsU01CA250554 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BERGER, BONNIE, YILMAZ, OMER · 2020 to 2022
$2.8M
Differential Wnt Dependencies in Colon Epithelium.K08CA277011 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI GEORGE ENG · 2023 to 2026
$785k
NCI NIH HHS K08 CA277011NCI NIH HHS R01 CA034992NCI NIH HHS R37 CA034992NCI NIH HHS U01 CA250554NIGMS NIH HHS P20 GM103430U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA034992U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) P20GM103430
6 · The paper itself

Abstract

A common mechanism by which cancer cells acquire resistance to chemotherapeutics is through the overexpression of efflux pumps, enabling the removal of cytotoxic agents, such as anthracycline drugs. However, platinum anticancer agents that crosslink DNA and interact with proteins are poor efflux pump substrates. Here, we design dual warhead drug conjugates by tethering a platinum pharmacophore to the doxorubicin backbone. These drug conjugates retain the anticancer activity of anthracyclines and exhibit the ability to both circumvent drug efflux and delay the acquisition of drug resistance. In vivo experiments demonstrate that such drug conjugates extend survival in a preclinical organoid-based model of metastatic colon cancer in mice. Mechanistic studies indicate that these drug conjugates overcome resistance through covalent platinum-protein interactions, leading to significantly improved drug retention and alteration of subcellular drug distribution. This application of platinum offers many opportunities to confront issues related to chemoresistance and alternative pathways for augmenting conventional chemotherapeutics.

Indexed as

Antineoplastic AgentsColonic NeoplasmsDrug Resistance, NeoplasmOrganoplatinum CompoundsPlatinumAnimalsCell Line, TumorDoxorubicinHumansMiceXenograft Model Antitumor AssaysAntineoplastic AgentsDoxorubicinOrganoplatinum CompoundsPlatinum

Identifiers

PMID41115858
PMCPMC12537935

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Registered trials

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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.