Anti-angiogenics currently used in
cancer therapy target angiogenesis by two major mechanisms: (i) neutralizing angiogenic factors or their receptors by using macromolecule
anti-angiogenic drugs (e.g., therapeutic
antibodies), and (ii) blocking intracellularly the activity of
receptor tyrosine kinases with small molecule (Mr < 1 kDa) inhibitors. Anti-angiogenics halt the growth and spread of
cancer, and significantly prolong the disease-free survival of the patients. However, resistance to treatment, insufficient efficacy, and toxicity limit the success of this antivascular
therapy. Published evidence suggests that four
albumin-
binding proteins (ABPs) (gp18, gp30, gp60/albondin, and secreted
protein acidic and
cysteine-rich (SPARC)) could be responsible for the accumulation of small molecule
receptor tyrosine kinase inhibitors (RTKIs) in normal organs and tissues and therefore responsible for the side effects and toxicity associated with this type of
cancer therapy. Drawing attention to these studies, this review discusses the possible negative role of
albumin as a
drug carrier and the rationale for a new strategy for
cancer therapy based on
follicle-stimulating hormone receptor (FSHR) expressed on the
luminal endothelial cell surface of peritumoral blood vessels associated with the major human
cancers. This review should be relevant to the audience and the field of
cancer therapeutics and angiogenesis/microvascular modulation-based interventions.