Angiogenesis is the process of formation of new blood vessels due to over expression of VEGF (vascular endothelial growth factor) which plays a critical role in the growth and development of all solid tumor types. With the advancement in understanding of tumor angiogenesis and VEGF, there have been a number of agents developed to target VEGF for the treatment of cancer. These targeted agents can affect downstream VEGF signal transduction by unique mechanisms at different cellular and extracellular levels. FDA has recently approved Aflibercept or VEGF-Trap in August 2012 for the treatment of colorectal cancer. It is a recombinant, decoy receptor fusion protein, rationally designed to block angiogenesis by targeting VEGF-A, VEGF-B and placental growth factor. VEGF-Trap exerts its antiangiogenic effects through regression of tumor vasculature, remodelling or normalization of surviving vasculature and inhibition of new tumor vessel growth. In this review, pre-clinical and clinical data have been summarized for aflibercept alone and in combination with chemotherapy to explore its efficacy and benefits in ovarian cancer, breast cancer, non-small cell lung cancer, pancreatic cancer, glioblastoma, adenocarcinoma and renal cell cancer xenograft models.
Prostate cancer is the most common malignancy among men found to be the second leading cause of male cancer-related mortality due to development of resistance against androgen deprivation therapy (ADT). With the advancement in understanding of prostate cancer, numbers of agents have been emerged to target Androgen-Receptor (AR) signaling for the treatment of castration resistant prostate cancer (CRPC). Food and Drug Administration (FDA) has recently approved enzalutamide (XTANDI) for the treatment of CRPC. Androgen receptor promotes the prostate cancer progression after transformation. Androgen receptor signaling leads to CRPC when cellular nucleus binds to DNA and increases pro cancer gene expression. In phase ΙΙΙ clinical trial, enzalutamide showed that 160 mg once daily oral administration is well tolerated and significantly enhanced overall survival in men with CRPC after chemotherapy, demonstrated by reduction in the serum prostate specific antigen (PSA) level and increased survival rate by 4.8 months.
Cabazitaxel has recently been approved by FDA for the treatment of docetaxel resistant hormone-refractory prostate cancer. It has been developed by Sanofi-Aventis under the trade name of Jevtana. It is given in combination with prednisone/prednisolone and has passed the clinical trial over well-known drug mitoxantrone. This drug is a microtubule depolymerization inhibitor, which can penetrate blood brain barrier (BBB). The FDA granted fast track designation to this drug in November 2009 and thereafter, new drug application submission was done in March 2010. Priority review to this drug was granted in April 2010 and finally in July 2010 it was approved by FDA. It is available in the form of injection in the dose of 60 mg/1.5 mL, which should be diluted prior to its use by the diluents supplied along with the injection. It is a second-line drug and has proven to be effective in patients experiencing docetaxel based treatment failure.
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