Molecular pathology of new anti-cancer agents and role of hlstopathologist in selecting these therapies [targeted therapy]

ABSTRACT

Since the Start of chemotherapy there has been a search for more specific anti-cancer agents which should selectively act against the tumor cells and spare the normal cells. We know that conventional anti-cancer drugs act against all dividing cells in our body and because of the fact that most of the tumor cells have high proliferative index they are at the selective disadvantage. There are two important considerations in this regard, firstly some tumor grow slowly rendering them less sensitive to these agents and paradoxically some normal cells divide very rapidly such as bone marrow, gut lining epithelium and hair follicle resulting in some of the well known side effects of chemotherapy such as myelosuppression, gastrointestinal disturbances and alopecia. With our better understanding of the molecular biology of cancer, new exploitable differences between normal and tumor cells have been discovered against which we can apply more specific agents. Majority of these molecular targets are protein products of oncogenes and oncosuppressor genes including growth factor receptors and their enzymatic intracytoplasmic domains. Various monoclonal antibodies directed against these proteins or small molecule inhibitors of their enzymatic intracytoplasmic domains are increasingly being used in cancer therapy such as imatinib mesylate, trastuzumab, cetuximab and gefitinib. This article reviews the molecular biology of these agents and the new and promising role of histopathologist in selecting these therapies for individual patients, known by various names such as targeted/customized/individualized or personalized therapy