Molecular Pathology of New Anti-cancer Agents And Role of Histopathologist 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
t a r g e t ed/c u stomi z ed/indiv idu a l i z ed or
personalized therapy