RESUMO
Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quinases Ciclina-Dependentes/antagonistas & inibidores , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Animais , Ciclo Celular/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Piperazinas/farmacologia , Piridinas/farmacologiaRESUMO
Breast cancer is a burden for western societies, and an increasing one in emerging economies, because of its high incidence and enormous psychological, social, sanitary and economic costs. However, breast cancer is a preventable disease in a significant proportion. Recent developments in the armamentarium of effective drugs for breast cancer prevention (namely exemestane and anastrozole), the new recommendation from the National Institute for Health and Care Excellence to use preventative drugs in women at high risk as well as updated Guidelines from the US Preventive Services Task Force and the American Society of Clinical Oncology should give renewed momentum to the pharmacological prevention of breast cancer. In this article we review recent major developments in the field and examine their ongoing repercussion for breast cancer prevention. As a practical example, the potential impact of preventive measures in Spain is evaluated and a course of practical actions is delineated.
Assuntos
Neoplasias da Mama/prevenção & controle , Antineoplásicos Hormonais/uso terapêutico , Proteína BRCA1/genética , Neoplasias da Mama/genética , Feminino , Humanos , Tamoxifeno/uso terapêuticoRESUMO
HER2-positive breast cancer, accounting for 15 % of the total breast cancer patient population, carries in itself a bad prognosis, which has now become much better after the advent of anti-HER2 drugs. HER2-targeted therapy has significantly improved disease free- and overall survival in HER2-positive breast cancer, and has rendered better disease control both in the early and advanced disease setting. Trastuzumab treatment duration is often prolonged and poses significant time and resource challenges both on the treatment institutions and on the patient. The recent development of a subcutaneous formulation has meant a significant advance in this respect. We review the drug development of the compound and the current evidence on its use.