Targeting the growth factors and angiogenesis pathways: Small molecules in solid tumors

Abstract

Research over the last decades has provided us with a better understanding of the biology of solid tumors. In some solid tumor malignancies single molecular events leading to malignant transformation have been identified, whilst in others multiple pathways seem to play a role simultaneously. The delineation of such pathways has led to the identification of therapeutic targets. Multiple compounds are available now to treat those molecular aberrations. With the wider use of newer biologic therapies, the understanding of biologic characteristics predicting a clinical response has broadened. This review focuses on the clinical management of gastrointestinal stromal tumors as well as hepatocellular, non small cell lung, renal cell and breast cancer with small molecule tyrosine kinase inhibitors, integrating some of the clinical advances with monoclonal antibody therapies in solid tumor malignancies. It highlights recent advances in relevant biomarkers to predict efficacy of biologic therapies and elaborates on their relevance in the clinical management of patients with solid tumor malignancies.

A new chemical inhibitor of angiogenesis and tumorigenesis that targets the VEGF signaling pathway upstream of Ras

“…Anti-angiogenic drugs such as anti-VEGF antibodies (Bevacizumab) and tyrosine kinase inhibitors (Sorafenib, Sunitinib, Pazopanib, …) have proven some efficacy in the treatment of several metastatic cancers [14, 15]. Since their beneficial effect is only observed in association with chemotherapy, their true mechanism of action in the patients is still a matter of debate [16–18].…”

Heme oxygenase 1 (HO-1) challenges the angiogenic switch in prostate cancer

“…Thus, anti-angiogenic therapy emerges as an essential strategy for the treatment of cancer [3]. However, angiogenesis is a complex process mediated by multiple factors (e.g., hypoxia, growth factors, cytokines and oxidative stress [30]) and thus it is essential to decipher the critical steps involved in this process in prostate cancer. We believe that our studies had identify new players in this process and thus open new opportunities for therapy development for prostate cancer.…”

Relationship between polymorphism of angiotensin-converting enzyme gene insertion/deletion and risk of hepatocellular carcinoma in a Chinese Dai population

“…3 Some studies have shown that tumor angiogenesis occurs at the early stage of tumor formation, which plays a vital role in promoting progressive tumor growth. [4][5][6] Any tumor, including HCC, depends on the formation of a vascular network to provide its with oxygen and essential nutrients. 5,6 The tumor that has not acquired its own new blood supply can not grow to more than a few millimeters in size.…”

“…[4][5][6] Any tumor, including HCC, depends on the formation of a vascular network to provide its with oxygen and essential nutrients. 5,6 The tumor that has not acquired its own new blood supply can not grow to more than a few millimeters in size. 4 Recent studies have demonstrated that angiotensin-converting enzyme (ACE), the regulator of the renin-angiotensin system (RAS), is overexpressed in several cancers including HCC, and directly involved in the process of cancer cell proliferation, differentiation, apoptosis, and angiogenesis.…”