Cell Cycle Dysregulation in Mantle Cell Lymphoma: Genomics and Therapy

Hematol Oncol Clin North Am. 2020 Oct;34(5):809-823. doi: 10.1016/j.hoc.2020.05.003. Epub 2020 Aug 1.

Abstract

Cell cycle dysregulation caused by aberrant cyclin D1 and CDK4 expression is a major determinant for proliferation of cancer cells in mantle cell lymphoma (MCL). Inhibition of CDK4/6 induces G1 arrest of MCL cells in patients, appearing to deepen and prolong the clinical response to partner agents. This article reviews aberrations of cell cycle genes in MCL cells and clinical trials of CDK4/6 inhibitors for MCL. Integrative longitudinal functional genomics is discussed as a strategy to discover genomic drivers for resistance in cancer cells and cancer-immune interactions that potentially contribute to the clinical response to palbociclib combination therapy in MCL.

Keywords: CDK4; Cyclin D1; Ibrutinib; Mantle cell lymphoma; Palbociclib; Rb; p16(INK4a).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cyclin D1* / genetics
  • Cyclin D1* / metabolism
  • Cyclin-Dependent Kinase 4* / genetics
  • Cyclin-Dependent Kinase 4* / metabolism
  • Cyclin-Dependent Kinase 6* / genetics
  • Cyclin-Dependent Kinase 6* / metabolism
  • G1 Phase Cell Cycle Checkpoints* / drug effects
  • G1 Phase Cell Cycle Checkpoints* / genetics
  • Genomics
  • Humans
  • Lymphoma, Mantle-Cell* / drug therapy
  • Lymphoma, Mantle-Cell* / genetics
  • Lymphoma, Mantle-Cell* / metabolism
  • Lymphoma, Mantle-Cell* / pathology
  • Piperazines / therapeutic use*
  • Pyridines / therapeutic use*

Substances

  • CCND1 protein, human
  • Piperazines
  • Pyridines
  • Cyclin D1
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib