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Taking Aim at the Undruggable.

Niamh Coleman1, Jordi Rodon1

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Scientists are developing new ways to target previously "undruggable" proteins in cancer. Recent advances are making difficult-to-drug targets, like RAS, more accessible for cancer therapy.

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Area of Science:

  • Oncology
  • Pharmacology
  • Biotechnology

Background:

  • The term "undruggable" describes proteins resistant to pharmacological targeting.
  • Cancer research faces challenges with elusive targets like STAT3, TP53, and MYC.
  • Developing drugs for these targets is a key goal in modern drug development.

Purpose of the Study:

  • To discuss recent technological and pharmacological advances eroding the concept of "undruggable" targets.
  • To highlight successes in targeting previously intractable proteins in cancer.
  • To explore future strategies for targeting difficult-to-drug proteins.

Main Methods:

  • Review of recent technologic and pharmacologic advances.
  • Discussion of successful drug development for previously undruggable targets.
  • Exploration of emerging technologies like proteolysis-targeting chimeras.

Main Results:

  • Erosion of the "undruggable" concept due to new technologies.
  • Successful targeting of previously intractable targets such as RAS (KRAS G12C, HRAS), HIF-2α, BCL-2, MDM2, and MLL.
  • Validation of new approaches for previously undruggable targets.

Conclusions:

  • Significant progress has been made in targeting proteins once considered undruggable.
  • Emerging technologies like proteolysis-targeting chimeras promise to revolutionize cancer target development.
  • The future of cancer drug development involves innovative strategies for previously intractable targets.