Recent data indicate a role for a pathway involved in controlling cell proliferation as a potential site for therapeutic intervention in breast cancer (BC). The concept of intervening in cell cycle control in cancer is not new, but has been borne out in preclinical studies, and is now offering real possibilities for treatment in women with BC who fail a commonly used endocrine therapy.An Essential Regulatory PathwayUnrestrained cell proliferation is a defining feature in cancer, and it is understood that, under normal conditions, this process is tightly regulated at many levels, one of which is the cell cycle.1,2 In a critical cell cycle ‘checkpoint’ mitogenic signals cause upregulation of cyclin D1, which binds to, and activates, cyclindependent kinases (CDKs) 4 and 6. CDKs 4 and 6, when activated, phosphorylate the retinoblastoma (Rb) protein, an event which causes its release from the E2F transcription factor.2,3 The release of E2F results in the transcriptional regulation of genes involved in the subsequent transition from the G1 phase of the cycle to the DNA synthesis (S) phase.2,3 Additional control is provided by inhibitors of CDK 4/6, such as p21 and p16.2Mateusz Opyrchal, MD, PhD, assistant professor of oncology at the Roswell Park Cancer Institute, Buffalo, New York, noted the considerable effort under way to examine the role of CDKs in oncogenesis and progression of cancers.“CDKs play an important role in regulating cell division, and they guide many processes before and during the cell division, making this a highly regulated process. In cancers, aberrations in CDK function, and specifically in the CDK 4/6 and Rb pathway, which regulates initiation of gene transcription, lead to increased cell proliferation and tumor growth, as well as resistance to treatments,” Opyrchal said. Early evidence for a role of the CDK 4/6 pathway in BC came from key findings, such as cyclin D1 overexpression and dysregulation of Rb function in BC.4,5 - See more at: targetedonc/publications/targeted-therapy-news/2014/sept-2014/concept-to-clinic-cdk-46-inhibition-in-er-positive-breast-cancer?__scoop_post=c9f4cee0-5b46-11e4-dbc6-001018304b75&__scoop_topic=3545156#__scoop_post=c9f4cee0-5b46-11e4-dbc6-001018304b75&__scoop_topic=3545156[...]
Posted on: Sat, 25 Oct 2014 12:22:33 +0000