[Sequential treatment with Mitomycin C and BCG in non muscle invasive bladder cancer.] / Tratamiento secuencial con Mitomicina C y BCG en el cáncer vesical no músculo-invasivo.

Bacilus Calmette-Guerin (BCG) administered intravesical is an effective therapy in non muscle invasive bladder cancer (NMIBC), but it presents limitations regarding recurrence and toxicity. For years, many case series have been published where sequential therapy with BCG and Mitomycin C (MMC) was tried. In this article, we perform a review of the data supplied by these articles with the aim to determine the safety and efficacy of combination, and what is the group of patients it should be indicated. Many studies show that combination therapy did not cause more toxicity and improved the interval free of disease with decrease of tumor progression compared to BCG or MMC monotherapy. Therefore, a combination of MMC and BCG therapy seems safe, but more clinical studies are required for a future evaluation.

[Castration resistance mechanisms in prostate cancer.] / Mecanismos de resistencia a la castración.

The androgen-signaling axis plays a pivotal role in the pathogenesis of prostate cancer. Since the landmark discovery by Huggins and Hodges, gonadal depletion of androgens has remained a mainstay of therapy for advanced disease. However, invariably progression to castration-resistant prostate cancer (CRPC) occurs within 2-3 years of initiation of ADT. Multiple mechanisms of resistance help contribute to the progression to castration resistant disease, and the androgen receptor (AR) remains an important driver in this progression. Molecular mechanisms behind AR reactivation in CRPC include AR gene amplification and overexpression, AR mutations, expression of constitutively active AR variants, intratumoral and adrenal androgen synthesis and promiscuous AR activation by other factors. Other AR-independent resistance mechanisms, including activation of glucocorticoid receptor, impairment of DNA repair pathways, immune-mediated resistance, neuroendocrine differentiation and microRNA expression, are also discussed. Castration-resistant prostate cancer is a complicated disease, characterized by multiple resistance mechanisms to androgen deprivation treatment, and it remains an incurable disease. An understanding of the mechanisms underlying this resistance is necessary to identify future therapeutic targets as well as the identification and validation of novel predictive biomarkers of resistance; they may lead to improved therapeutics for mCRPC patients.