Drug discovery oases

Predictive validity in drug discovery: what it is, why it matters and how to improve it

Find out why the predictive validity of tools used for decision-making in drug R&D is more important than typically appreciated in this Perspective in the December issue 

  • Jack W. Scannell
  • James Bosley
  • J. Mark Treherne
Perspective

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    • The potential of therapeutically targeting phosphoinositide kinases (PIKs) beyond the class I PI3Ks is increasingly being realized. Here, Burke et al. describe the structure, function, regulation and roles in disease of all clinically relevant PIKs outside of the class I PI3Ks, assessing potent and specific small-molecule inhibitors in development.

      • John E. Burke
      • Joanna Triscott
      • Gerald R. V. Hammond
      Review Article
    • The discovery of the monoclonal antibody trastuzumab almost 25 years ago revolutionized treatment and drug development for HER2+ breast cancer. Here, Swain et al. review the current standard of care for HER2+ breast cancer, describe mechanisms of drug resistance and focus on next-generation platforms and therapies for the treatment of this disease.

      • Sandra M. Swain
      • Mythili Shastry
      • Erika Hamilton
      Review Article
    • Studies of human genetics have been used to identify promising drug targets, and might also inform safety assessment in the drug discovery process. In their Review, Ward and co-authors from industry discuss how genetic studies of rare and complex human diseases can be used to predict potential on- and off-target effects associated with modulating a given target. They also outline suggested best practices for incorporating human genetic data into safety assessments during drug development.

      • Keren J. Carss
      • Aimee M. Deaton
      • Jing Yuan
      Review Article
    • Tumour suppressor gene TP53 is frequently mutated in cancer, and therapeutic strategies to restore the functionality of p53 in tumours have been pursued for decades without success. This Review discusses the promising approaches towards p53-based therapy that have emerged in recent years.

      • Ori Hassin
      • Moshe Oren
      Review Article
    • Replication stress is a cause of genome instability in cancer cells. This Review discusses strategies to increase replicative stress by inhibiting the checkpoint kinases that coordinate DNA damage response and cell cycle, as well as combination strategies with other targeted therapies.

      • Alexandre André B. A. da Costa
      • Dipanjan Chowdhury
      • Panagiotis A. Konstantinopoulos
      Review Article

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