Recent advances in the treatment of castration-resistant prostate cancer (CRPC) have started to change the therapeutic landscape allowing clinicians to choose from a broad range of treatment options. Understanding the mechanisms that transform prostate cancer (PCA) into a castration-resistant state has enabled investigators to explore critical pathways involved in such process allowing for rational therapeutic design. These novel therapies complement the modest success that chemotherapy has demonstrated in recent years. In this review, we discuss the different mechanisms that render PCA castration resistant and elaborate on the nonchemotherapy approaches evolving in CRPC. These include agents targeting the epidermal growth factor receptor, endothelin receptor antagonists, angiogenesis inhibitors, immunomodulatory agents, immunotherapy, novel antiandrogens, and delivery of cytotoxic agents via therapeutic antibodies. This timely review coincides with the identification of newer therapies in this setting affirming our steady movement towards better disease control.
Bruton tyrosine kinase plays a critical role in hastening cell proliferation. Bruton tyrosine kinase inhibitors are a class of immunotheraputic agents that disrupt this signaling pathway. Ibrutinib, a novel Bruton tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of Waldenstrom macroglobulinemia in patients who have failed treatment with other agents, has emerged as an important therapeutic agent in the management of Waldenstrom macroglobulinemia and other plasma cell dyscrasias. Ibrutinib has shown to increase progression free survival and improve overall mortality. We present a review of ibrutinib, beginning with an overview of the Bruton tyrosine kinase pathway and clinically relevant gene mutations impacting treatment and prognosis for patients with Waldenstrom macroglobulinemia, followed by evidence supporting therapeutic indications for ibrutinib, and detailing its safety and efficacy evidence, current clinical guidelines, adverse effects and their management, and finally challenges of drug resistance. We also present findings on newly developed Bruton tyrosine kinase inhibitors in the therapeutic pipeline to provide readers insight into this rapidly evolving corner of oncology pharmacy practice.
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