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Editorial
. 2018 Mar 1;29(3):535-537.
doi: 10.1093/annonc/mdy017.

Circulating tumour DNA analyses reveal novel resistance mechanisms to CDK inhibition in metastatic breast cancer

C Abbosh  1 , C Swanton  2 , N J Birkbak  3
Affiliations
Editorial

Circulating tumour DNA analyses reveal novel resistance mechanisms to CDK inhibition in metastatic breast cancer

C Abbosh et al. Ann Oncol. .
No abstract available

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Figures

Figure 1.
Figure 1.
Cell cycle progression through E2F regulation, and the role of CDK and estrogen (ER) inhibitors. Transcriptional activation of cyclin-D1 (CCND1) through the estrogen receptor (ESR1), promotes dimerization of CCND1 and CDK4, and CCND1 and CDK6, escaping inhibition by p16. The cyclin-D/CDK complex phosphorylates Rb, releasing E2F to promote cell cycle progression through transcriptional activation of S-phase and G2/M gene sets. Additional transcriptional activation through E2F induction may affect genes involved in DNA methylation and PD-L1 expression. Pharmacological inhibition of ER and CDK4/6 synergistically affects downstream activation of E2F and inhibits cell cycle progression in the context of wild-type Rb. Mutational inactivation of Rb promotes therapeutic resistance.
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References

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