Chapter 1 - Potential physical and biological barriers leading to failure of cancer chemotherapy

Abstract

Cancer is among the deadliest diseases in the world, with millions of new cases reported each year. Chemotherapy is preferred for cancer treatment due to the invasive nature of and other problems associated with surgery, laser therapy, and photodynamic therapy. Currently used chemotherapeutic agents face various issues that limit their effective use for cancer treatment. These issues arise either from the physicochemical properties or biological barriers associated with the tumor microenvironment or biological systems. The physicochemical barriers are associated with the anticancer drugs and include their lower aqueous solubility and membrane permeability, nonselectivity toward cancerous cells, and instability in the intestine due to harsh acidic and enzymatic actions. The biological barriers that reduce the therapeutic efficacy of anticancer drugs include transmembrane drugs’ efflux transporter proteins, presystemic metabolism, nonlinear pharmacokinetics, hepatic impairment and malabsorption, genetic variations, physiological characteristics of tumor tissues and their unique microenvironment, and impediments erected by the blood–brain barrier for successful treatment of brain tumors. This chapter covers both the physicochemical and biological barriers that reduce the therapeutic efficacy of chemotherapeutic agents used for the treatment of various types of cancers.