Cell-cycle reprogramming for Pi3K inhibition overrides a relapse-specific C481s BTK mutation revealed by longitudinal functional genomics in mantle cell lymphoma Academic Article uri icon


MeSH Major

  • Cell Cycle
  • Genomics
  • Lymphoma, Mantle-Cell
  • Mutation
  • Phosphatidylinositol 3-Kinases
  • Protein-Tyrosine Kinases


  • We have discovered the first relapse-specific BTK mutation in patients with MCL with acquired resistance, but not primary resistance, to ibrutinib, and demonstrated a rationale for targeting the proliferative resistant MCL cells by inhibiting CDK4 and the cell cycle in combination with ibrutinib in the presence of BTK(WT) or a PI3K inhibitor independent of BTK mutation. As drug resistance remains a major challenge and CDK4 and PI3K are dysregulated at a high frequency in human cancers, targeting CDK4 in genome-based combination therapy represents a novel approach to lymphoma and cancer therapy. Cancer Discov; 4(9); 1022-35. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 973.

publication date

  • January 2014



  • Academic Article



  • eng

PubMed Central ID

  • PMC4155003

Digital Object Identifier (DOI)

  • 10.1158/2159-8290.CD-14-0098

PubMed ID

  • 25082755

Additional Document Info

start page

  • 1022

end page

  • 35


  • 4


  • 9