# Drugging the 'undruggable' cancer targets

Source: https://onco.cc/key-papers/paper-dang-nat-rev-cancer/  
OnCo record `paper-dang-nat-rev-cancer` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one bottleneck page and 24 idea pages, indexed on Europe PMC as PubMed record 28643779 and published in Nature Reviews Cancer; the citing pages link this DOI, which is how the record was matched.

## Summary

The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies. In this Viewpoint article, we asked four scientists working in this field for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of research.

Indexed on Europe PMC as PubMed record 28643779 (DOI 10.1038/nrc.2017.36). Matched by DOI alone: one bottleneck page and 24 idea pages cite this DOI among their external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Nature Reviews Cancer
- Year: 2017
- DOI: 10.1038/nrc.2017.36
- Authors: Dang CV, Reddy EP, Shokat KM, et al.
- What it means: One bottleneck page and 24 idea pages on OnCo cite this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing pages listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Nat Rev Cancer 2017: https://doi.org/10.1038/nrc.2017.36
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28643779/
- Europe PMC: https://europepmc.org/article/MED/28643779

## Connected records

- bottlenecks: [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/)
- ideas: [A guaranteed purchase prize for the first drug against a named hard target](https://onco.cc/ideas/idea-bio1-undruggable-market-commitment/), [AI-designed proteins that grip the floppy parts of cancer drivers](https://onco.cc/ideas/idea-bio1-ai-binders-disordered-regions/), [An open map of which cancer proteins any drug can stick to](https://onco.cc/ideas/idea-bio1-covalent-ligandability-atlas/), [Antibodies that see mutant KRAS and p53 fragments displayed on the cell surface](https://onco.cc/ideas/idea-bio1-pmhc-bispecifics-public-drivers/), [Attack the backup copy when a tumour has lost the original gene](https://onco.cc/ideas/idea-bio1-paralog-synthetic-lethality/), [Break up the liquid droplets where oncogenic transcription happens](https://onco.cc/ideas/idea-bio1-condensate-disruptors/), [Covalent chemistry for the RAS mutations that still have no drug](https://onco.cc/ideas/idea-bio1-pan-ras-covalent-g12d/), [Degrade the damaged p53 protein rather than trying to repair it](https://onco.cc/ideas/idea-bio1-mutant-p53-degrader/), [Degraders for the fusion proteins that drive childhood sarcomas](https://onco.cc/ideas/idea-bio1-fusion-tf-degraders/), [Destroy the truncated androgen receptor that hormone drugs cannot touch](https://onco.cc/ideas/idea-bio1-arv7-degrader/), [Drag cancer's surface and secreted proteins to the cell's recycling bin](https://onco.cc/ideas/idea-bio1-lytac-surface-degraders/), [Extend p53 reactivation beyond the Y220C mutation](https://onco.cc/ideas/idea-bio1-p53-mutant-reactivator-expansion/), [Find E3 ligases that only tumours have, and build degraders around them](https://onco.cc/ideas/idea-bio1-tumour-restricted-e3-atlas/), [Instruct tumour cells to make antibodies against their own oncoprotein](https://onco.cc/ideas/idea-bio1-mrna-intrabodies/), [Macrocyclic peptides to cover protein surfaces that pills cannot](https://onco.cc/ideas/idea-bio1-macrocycle-ppi-campaign/), [Molecular glues that break the MYC-MAX partnership](https://onco.cc/ideas/idea-bio1-myc-max-molecular-glue/), [mRNA-delivered MYC decoy proteins instead of MYC inhibitors](https://onco.cc/ideas/idea-bio1-omomyc-mrna/), [Screen glue-like compounds against every cancer cell line and publish it](https://onco.cc/ideas/idea-bio1-glue-degrader-atlas/), [Small molecules that cut the RNA message of an undruggable oncogene](https://onco.cc/ideas/idea-bio1-rna-targeting-small-molecules/), [Starve MYC-driven tumours by blocking protein production machinery](https://onco.cc/ideas/idea-bio1-translation-dependency-myc/), [Switch off an undruggable oncogene permanently with epigenetic editing](https://onco.cc/ideas/idea-bio1-epigenetic-silencing-in-vivo/), [Turn a brake back on: drugs that reactivate the PP2A phosphatase](https://onco.cc/ideas/idea-bio1-pp2a-activators/), [Use antibodies to deliver protein-destroying drugs into the right cells](https://onco.cc/ideas/idea-bio1-antibody-degrader-conjugates/), [WRN inhibitors: a second synthetic-lethal win for mismatch-repair cancers](https://onco.cc/ideas/idea-bio1-wrn-msi-programme/)
- journals: [Nature Reviews Cancer](https://onco.cc/journals/nature-reviews-cancer/)

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