Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr;11(4):815-821.
doi: 10.1158/2159-8290.CD-21-0260.

Emerging Trends in Cancer Drug Discovery-From Drugging the "Undruggable" to Overcoming Resistance

Joachim Rudolph  1 , Jeff Settleman  2 , Shiva Malek  3
Affiliations

Emerging Trends in Cancer Drug Discovery-From Drugging the "Undruggable" to Overcoming Resistance

Joachim Rudolph et al. Cancer Discov. 2021 Apr.

Abstract

Technology advancement and the courage to challenge dogma have been key elements that have continuously shifted druggability limits. We illustrate this notion with several recent cancer drug-discovery examples, while also giving an outlook on the opportunities offered by newer modalities such as chemically induced proximity and direct targeting of RNA. Treatment resistance is a major impediment to the goal of durable efficacy and cure, but the confluence of new biological insights, novel drug modalities, and drug combinations is predicted to enable transformative progress in this decade and beyond.

PubMed Disclaimer

References

    1. Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov. 2002;1:727–30.
    1. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Drugging the undruggable RAS: mission possible?. Nat Rev Drug Discov. 2014;13:828–51.
    1. Berndt N, Hamilton AD, Sebti SM. Targeting protein prenylation for cancer therapy. Nat Rev Cancer. 2011;11:775–91.
    1. Ostrem JM, Peters U, Sos ML, Wells JA, Shokat KM. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature. 2013;503:548–51.
    1. Lanman BA, Cee VJ, Marx MA. Clinical and preclinical approaches to the inhibition of KRASG12C. Med Chem Rev. 2020;55:249–71.

Substances