Antiangiogenic therapy: impact on invasion, disease progression, and metastasis

Abstract

Antiangiogenic drugs targeting the VEGF pathway have slowed metastatic disease progression in some patients, leading to progression-free survival (PFS) and overall survival benefits compared with controls. However, the results are more modest than predicted by most preclinical testing and benefits in PFS are frequently not accompanied by overall survival improvements. Questions have emerged about the basis of drug resistance and the limitations of predictive preclinical models, and also about whether the nature of disease progression following antiangiogenic therapy is different to classic cytotoxic therapies—in particular whether therapy may lead to more invasive or metastatic behavior. In addition, because of recent clinical trial failures of antiangiogenic therapy in patients with early-stage disease, and the fact that there are hundreds of trials underway in perioperative neoadjuvant and adjuvant settings, there is now greater awareness about the lack of appropriate preclinical testing that preceded these studies. Improved preclinical assessment of all stages of metastatic disease should be a priority for future antiangiogenic drug discovery and development.

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…Targeting these factors has become a focal point in developing new drug therapies and improving upon existing treatments such as VEGFdependent antiangiogenic agents which have moderate impact as monotherapies [115]. Formation of new blood vessels to fuel tumor growth depends upon the interaction of the cancer cells with the TME angiogenic components, i.e.…”

CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis

“…A ngiogenesis is a rate-limiting step in the development of many solid tumors, making it an attractive target for therapeutic intervention (1). Although pharmacologic modulation of angiogenesis has shown some clinical success, negative factors such as treatment-related plasticity, drug resistance, and tumor diversity have underscored the need for a better understanding of tumor-associated blood vessel formation at a mechanistic level (2). Tumor angiogenesis is a multifactorial process involving several different cell subtypes, especially tumor stromal endothelial cells, pericytes, carcinoma-associated fibroblasts (CAFs), and bone marrow-derived cells (BMDCs) (3,4).…”

Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

“…Options include elimination or suppression of the CSCs in the niche; blocking the interaction between the CSCs and stromal cells; impeding the generation of the niche factors by both tumor and stromal cells; and using new approaches to hinder tumor neovascularization and to normalize the disorganized tumor blood vessels as we have recently addressed [95]. Solid tumors require blood vessels for generation of the CSC niche, growth, and metastasis; therefore, the tumor vasculature has been targeted using anti-angiogenic drugs to decrease the tumor vascular supply, but the success of antiangiogenesis at the early stage is limited by insufficient efficacy and development of drug resistance [96][97][98]. Normalization of the vascular abnormalities is a complementary therapeutic approach for cancer [99][100][101].…”