Resistance of melanoma cells to anticancer treatment: a role of vascular endothelial growth factor

Abstract

A b s t r a c tMelanoma is one of the most aggressive and resistant to treatment neoplasms. There are still many challenges despite many promising advances in anticancer treatment. Currently, the main problem for all types of treatment is associated with heterogeneity. Due to heterogeneity of cancer cells, "precise" targeting of a medicine against a single phenotype limits the efficacy of treatment and affects resistance to applied therapy. Therefore it is important to understand aetiology and reasons for heterogeneity in order to develop effective and long-lasting treatment. This review summarises roles of vascular endothelial growth factor (VEGF) that may stimulate growth of a melanoma tumour irrespective of its proangiogenic effects, contributing to cancer heterogeneity. VEGF triggers processes associated with extracellular matrix remodelling, cell migration, invasion, angiogenesis, inhibition of immune responses and favours phenotypic plasticity and epithelial-mesenchymal transition. Consequently, it participates in mechanisms of interactions between melanoma cancer cells and microenvironment and it can modify sensitivity to therapeutic factors.

Vitamin D Enhances Anticancer Properties of Cediranib, a VEGFR Inhibitor, by Modulation of VEGFR2 Expression in Melanoma Cells

“…Therefore, antiangiogenic therapies in melanoma are rather supportive to other forms of treatment. However, various configurations of combination therapies with antiangiogenic bevacizumab against melanoma are currently being investigated in clinical trials (73). Very interestingly, as documented recently by Atzori (74), VEGFR1 inhibition might potentiate the effects of vemurafenib-based therapies for melanoma treatment and, what is more, counteract resistance development to this BRAF inhibitor, since the latter was associated with higher expression of VEGF receptors.…”

“…On the other hand, in MNT-1 and RPMI-7951 melanoma cells, in which we did not observe any enhancement of cediranib cytotoxicity by supplementation with vitamin D, we did detect any VEGFR2 protein in the experimental conditions used. It should be noted that VEGFR2 is considered a predominant receptor triggering VEGF signaling in cells (73,79). Out of the three primary VEGF receptors, VEGFR2 is considered the dominant effector and the most relevant in the metastatic melanoma microenvironment, although the study of Molhoek and coworkers showed that a relatively low percentage of melanoma cells express VEGFR2 (80).…”

The Therapeutic Effect of Myrrh (Commiphora molmol) and Doxorubicin on Diethylnitrosamine Induced Hepatocarcinogenesis in Male Albino Rats

“…VEGF is the central growth factor and the main regulator facilitating the angiogenesis of HCC (Bogusławska-Duch et al, 2020). Basa et al, (2011) stated that the immunohistochemical expression of VEGF is increased in 87.7% of HCC cells.…”

Resistance to Molecularly Targeted Therapies in Melanoma

“…The development of novel therapies is crucial for improving treatment of this aggressive disease [ 194 ]. Given the crucial role of VEGF in tumor growth and metastasis, additional research is necessary to improve the efficacy of current anti-VEGF therapies, as well as to further elucidate the role of VEGF in extracellular matrix remodeling, cell migration, invasion, and inhibition of immune responses [ 196 ].…”