RESUMEN
It has now been 15 years since the HER2-targeted monoclonal antibody trastuzumab was introduced in clinical and revolutionized the treatment of HER2-positive breast cancer patients. Despite this achievement, most patients with HER2-positive metastatic breast cancer still show progression of their disease, highlighting the need for new therapies. The continuous interest in novel targeted agents led to the development of pertuzumab, the first in a new class of agents, the HER dimerization inhibitors. Pertuzumab is a novel recombinant humanized antibody directed against extracellular domain II of HER2 protein that is required for the heterodimerization of HER2 with other HER receptors, leading to the activation of downstream signalling pathways. Pertuzumab combined with trastuzumab plus docetaxel was approved for the first-line treatment of patients with HER2-positive metastatic breast cancer and is currently used as a standard of care in this indication. In the neoadjuvant setting, the drug was granted FDA-accelerated approval in 2013. Pertuzumab is also being evaluated in the adjuvant setting. The potential of pertuzumab relies in the dual complete blockade of the HER2/3 axis when administered with trastuzumab. This paper synthetises preclinical and clinical data on pertuzumab and highlights the mechanisms underlying the synergistic activity of the combination pertuzumab-trastuzumab which are essentially due to their complementary mode of action.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Trastuzumab/uso terapéutico , Neoplasias de la Mama/química , Neoplasias de la Mama/patología , Docetaxel , Femenino , Humanos , Receptor ErbB-2/antagonistas & inhibidores , Taxoides/uso terapéuticoRESUMEN
To make up for the lack of data on (210)Pb aerosol deposition in tropical regions and to use this radionuclide as an aerosol tracer, a monitoring station was run for two years at Petit-Saut, French Guiana. Lead-210 concentration in air at ground level was monitored continuously together with atmospheric total deposition. The air concentration has a mean value of 0.23+/-0.02 mBq m(-3) during both wet and dry seasons, and it is only weakly affected by the precipitation mechanism. This result was unexpected in a wet tropical region, with a high precipitation rate. In contrast, deposition clearly correlates with precipitation for low/moderate rainfall (<15 cm per 15-day), while this correlation is masked by strong fluctuations at high rainfall. The estimated mean annual deposition over the last ten years is 163+/-75 Bq m(-2) y(-1). This provides a procedure for estimating this mean flux at other sites in French Guiana.