Understanding the Microenvironment of Melanoma Cells for the Development of Target Drug Delivery Systems

*Lucas B. Naves,1,2,3 Luis Almeida,2 Seeram Ramakrishna,3,4

1. CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil
2. Centre for Textile Science and Technology, University of Minho, Guimarães, Portugal
3. Center for Nanofibers & Nanotechnology, Department of Mechanical Engineering, National University of Singapore, Singapore
4. Guangdong-Hong Kong-Macau Institute of CNS Regeneration (GHMICR), Jinan University, Guangzhou, China
*Correspondence to dinoeh@hotmail.com

Disclosure: The authors have declared no conflicts of interests.
Acknowledgements: The authors want to acknowledge financial support from the CAPES foundation for the PhD grant (process number: 13543/13-0), Brazilian Ministry of Education, Brazil. The authors would also like to thank FEDER funds through the Competitivity Factors Operational Programme – COMPETE – and national funds through FCT – Foundation for Science and Technology [POCI- 01-0145-FEDER-007136].
Received: 19.04.17 Accepted: 21.09.17
Citation: EMJ Oncol. 2017;5[1]:85-92.

Abstract

Melanoma is the most aggressive and deadly form of skin cancer. The high rate of patient death is related to advanced melanoma metastasis, which usually occurs several months to years after the primary melanoma diagnosis. At an early stage, the melanoma tumour can be removed, therefore promoting a survival rate up to 99%. In this manuscript, we elucidate the tumour microenvironment factor, which is crucial for melanoma growth, proliferation, and metastasis. Melanoma is more resistant to traditional therapies, such as chemotherapy and radiotherapy; indeed, tumour-associated macrophages are often related to the worst prognosis. A better understanding of the melanoma microenvironment, including melanoma-associated fibroblasts and hypoxia-inducible factors, will enable researchers to develop drug-delivery systems with higher anticancer activity than current melanoma therapies available on the market. This review also covers macrophage targeting melanoma, such as macrophage colony-stimulating factor receptor inhibitors, C-C chemokine ligand 2 inhibitors, and vaccines combining αFAP-PE38 and melanoma associated antigens via lentiviral vectors. We also report a study using statins, which demonstrated long circulating liposome-encapsulate simvastatin reduced tumour-associated macrophagemediated oxidative stress and production of the hypoxia-inducible factor 1α in tumours. In melanoma, xenografts may be treated with antiangiogenic agents targeting different angiogenic pathways, such as properdistatin, which selectively removes small diameter vessels and reduces the blood supply time. Sunitinib also plays a role in reducing the density of small and large diameter vessels, although it does not change the blood supply time. Considering all these factors holistically suggests that a better understanding of the melanoma microenvironment is crucial for the development of a novel and effective therapeutic approach.

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