Introduction: Cyclin-dependent kinases (CDK) represent attractive targets in oncology due to their key role in controlling gene transcription and cell cycle progression. Dinaciclib (MK-7965, formerly SCH727965) is a relatively novel CDK 1/2/5/9 inhibitor that has shown promising results in preclinical studies and an acceptable safety profile in Phase I clinical trials. It is currently under clinical evaluation for the treatment of hematological and solid malignancies, including breast cancer.Areas covered: This review summarizes the current understanding of CDK's role in physiology and cancer, and the therapeutic value of blocking their pathways in breast cancer. Particularly, the article reviews the preclinical and clinical data for dinaciclib in its use for the treatment of breast cancer.Expert opinion: A better understanding of the molecular mechanisms underlying cell cycle dysregulation in cancer is needed in order to develop novel CDK inhibitors. Additionally, further efforts are needed to identify potential biomarkers of dinaciclib efficacy, which could allow a better selection of patients enrolled in clinical trials. Moreover, combination therapies with dinaciclib or other CDK and chemotherapy, endocrine therapy or targeted therapies might be further evaluated in breast cancer patients.

Dinaciclib for the treatment of breast cancer / C. Criscitiello, G. Viale, A. Esposito, G. Curigliano. - In: EXPERT OPINION ON INVESTIGATIONAL DRUGS. - ISSN 1354-3784. - 23:9(2014), pp. 1305-1312.

Dinaciclib for the treatment of breast cancer

C. Criscitiello;G. Viale;G. Curigliano
Writing – Original Draft Preparation
2014

Abstract

Introduction: Cyclin-dependent kinases (CDK) represent attractive targets in oncology due to their key role in controlling gene transcription and cell cycle progression. Dinaciclib (MK-7965, formerly SCH727965) is a relatively novel CDK 1/2/5/9 inhibitor that has shown promising results in preclinical studies and an acceptable safety profile in Phase I clinical trials. It is currently under clinical evaluation for the treatment of hematological and solid malignancies, including breast cancer.Areas covered: This review summarizes the current understanding of CDK's role in physiology and cancer, and the therapeutic value of blocking their pathways in breast cancer. Particularly, the article reviews the preclinical and clinical data for dinaciclib in its use for the treatment of breast cancer.Expert opinion: A better understanding of the molecular mechanisms underlying cell cycle dysregulation in cancer is needed in order to develop novel CDK inhibitors. Additionally, further efforts are needed to identify potential biomarkers of dinaciclib efficacy, which could allow a better selection of patients enrolled in clinical trials. Moreover, combination therapies with dinaciclib or other CDK and chemotherapy, endocrine therapy or targeted therapies might be further evaluated in breast cancer patients.
Breast cancer; Cyclin-dependent kinases; Cyclin-dependent kinases inhibitors; Dinaciclib; Pharmacology; Pharmacology (medical)
Settore MED/06 - Oncologia Medica
2014
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/553461
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