Abstract
Unexpected outcomes of CDK4/6 inhibition.
Highlights
The response of cells to extracellular mitogenic signals and commitment to enter G1 phase, are regulated by the D-type cyclins (D1, D2 and D3)
Cyclin D3 is highly expressed in several hematopoietic malignancies, such as T-cell acute lymphoblastic leukemias (T-ALL)
Several groups have shown that mice lacking cyclin D1, or lacking CDK4, or expressing kinase-inactive cyclin D1-CDK complexes are either completely resistant, or show significantly reduced susceptibility to HER2-driven breast cancers, depending on the genetic background used
Summary
The response of cells to extracellular mitogenic signals and commitment to enter G1 phase, are regulated by the D-type cyclins (D1, D2 and D3). Recent analyses using mouse cancer models revealed unexpected outcomes of cyclin D-CDK kinase inhibition in vivo, in tumor bearing mice. Several groups have shown that mice lacking cyclin D1, or lacking CDK4, or expressing kinase-inactive cyclin D1-CDK complexes are either completely resistant, or show significantly reduced susceptibility to HER2-driven breast cancers, depending on the genetic background used (see references in [3]).
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