Immunohistochemistry for Assessing Toxicity and Mechanism of Action of Anticancer Drugs During Preclinical Trials. Part II. Cell Death, Vasculogenesis and Angiogenesis

Abstract

About 120 chemical compounds are registered in Russia as anticancer drugs, and screening and investigation of novel therapies remain an urgent task for specialists in pathophysiology, pharmacology and oncology. Among them, treatments targeting neovascularisation and regulated cell death of atypical cells within the malignant tumours are of utmost importance. Hence, development of novel anti-cancer drugs must include testing of their pro-apoptotic and anti-angiogenic activity. Here we review the markers of angiogenesis and regulated cell death during the tumor development and the respective immunohistochemical applications for preclinical trials. Here we discuss relevant molecular markers for studying primary cell death subroutines which can be targeted by anticancer agents. The most sensitive and specific immunohistochemical markers of programmed cell death are tumor necrosis factor alpha (TNF-α) for necrosis and anti-cellular apoptosis susceptibility/CSE1L, Bcl-2, and apoptotic protease activating factor-1 (APAF1) for apoptosis. Primary markers of angiogenesis include vascular endothelial growth factor A (VEGF-A), hypoxia-inducible factor 1-alpha (HIF-1α), and platelet-derived growth factor (PDGF). Analysis of tumour blood supply, metastasis and apoptosis has both theoretical and practical significance with direct implications for the pharmaceutical industry.