Abbosh, C;
Swanton, C;
Birkbak, NJ;
(2018)
Circulating tumor DNA analyses reveal novel resistance mechanisms to CDK inhibition in metastatic breast cancer.
Annals of Oncology
10.1093/annonc/mdy017.
(In press).
Preview |
Text
mdy017.pdf - Published Version Download (288kB) | Preview |
Abstract
Cyclin-dependent kinase (CDK) 4/6 inhibition has been demonstrated to improve progression-free survival (PFS) in patients with human epidermal growth factor receptor 2 (HER2−), hormone receptor positive (HR+) in advanced breast cancer [1–3]. Palbociclib, ribociclib and abemaciclib are orally bioavailable selective CDK 4/6 inhibitors. These small molecules likely bind the ATP-binding pocket within the CDK4/6 protein kinases thereby inhibiting phosphorylation of retinoblastoma tumour suppressor protein (Rb). In its hypophosphorylated state Rb remains bound to E2F thereby preventing progression through the G1-S-cell cycle checkpoint [4]. The mechanism behind the observed efficacy of CDK inhibition in metastatic breast cancer may relate to a dependence of HR+ breast cancer on CDK4/6 activity to override Rb mediated repression of cell cycle progression (Figure 1) [5].
| Type: | Article |
|---|---|
| Title: | Circulating tumor DNA analyses reveal novel resistance mechanisms to CDK inhibition in metastatic breast cancer |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1093/annonc/mdy017 |
| Publisher version: | http://doi.org/10.1093/annonc/mdy017 |
| Language: | English |
| Additional information: | Copyright © The Author(s) 2018. Published by Oxford University Press on behalf of the European Society for Medical Oncology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10044560 |
Archive Staff Only
 |
View Item |
