Targeted therapies, aspects of pharmaceutical and oncological management

Abstract

A revolution is underway in cancer therapy and care. Now, based on identifying in a patient’s cancer those genetic alterations that drive cancer growth, use of cancer therapy is more targeted and cancer care is more personalised. Many genetic alterations are ‘passenger mutations’ in the oncogenic process, but other ‘driver mutations’ promote cancer growth and survival. These harmful genetic alterations usually result in the production of abnormal proteins such as V600-mutant BRAF in melanoma, or in the overproduction of normal proteins such as HER2 in breast cancer. In drug development, the abnormal or excess proteins are described as ‘druggable targets’, and drugs developed to selectively inhibit the function of these proteins are called ‘targeted therapies’. Since a driver mutation can be found in more than one different type of cancer, an approved and available targeted therapy can make the mutation ‘clinically actionable’. Examples of targeted therapies include the small-molecule drug, vemurafenib (ZelborafR), for advanced V600-mutant BRAF melanoma, and the monoclonal antibody, trastuzumab (Herceptin®), for HER2-positive breast cancer. Although targeted therapies are generally considered less toxic than conventional cytotoxic chemotherapy, the toxicities may be problematic and dose limiting. However, careful clinical management of these toxicities can allow patients to continue to receive effective therapy.