• “The role of the microenvironment: Models for the study of melanoma”.

LUCIA SPERONI, VICTORIA DE LOS ANGELES BUSTUOABAD, JULIETA GASPARRI, NADIA SILVIA CHIARAMONI, MARÍA CRISTINA TAIRA, RAÚL ALEJANDRO RUGGIERO, SILVIA DEL VALLE ALONSO

Breakthroughs in Melanoma Research.

INTECH Open Access Publisher

Lugar: Rijeka; Año: 2011; p. 33 - 42

Melanoma is a progressive disease that claims many lives each year due to lack oftherapeutics effective for the long-term treatment of patients. Currently, the best treatmentoption is early detection followed by surgical removal. Cutaneous melanoma continues torepresent both a challenge and a big paradox among solid tumors: though considerableprognostic markers are available, little is known about their biological significance. Recentdata on the effect of an anti-melanoma target therapy, ipilimumab (Hodi et al, 2010) and new anti-BRAF molecules (Flaherty, 2010) raised hope on the treatment of melanoma. However, although response rates with small molecule inhibitors are high, most are not durable.Moreover, for a large subset of patients, reliable predictive biomarkers especially forimmunologic modulators have not yet been identified. Progress on the treatment of bothearly and advanced melanoma may depend on identifying additional molecular targets andon understanding the mechanisms leading to response or resistance.Animal models have been critical in the study of the molecular mechanisms of cancer and in the development of new therapeutic agents; nevertheless, there is still much room forimprovement. The most widely used in vivo model involves the injection of tumor cells inthe flank of mice. The relevance of each particular model depends on how close it replicates the histology, physiological effects, biochemical pathways and metastatic pattern observed in the same human tumor type. Numerous models have been developed to study human tumorigenesis and its properties, such as proliferation, migration, invasion, neoangiogenesis, and metastasis, as well as for the study of anti-cancer treatments. Among others, these include in vitro systems such as focus formation in tumor cell culture explants and continuous cell lines grown on tissue culture plates, or, alternatively, anchorage-independent growth in soft agar. The foregoing experimental models are suitable for studying molecular pathways in cell-cell and cell-extracellular matrix interactions that would be difficult to dissect in the animal. However they will encounter their limitation in terms that they are not particularly amenable to the investigation of interactions of tumor cells with the surrounding microenvironment of adjacent normal human cell tissues and structures. It has been shown that tumor progression is associated with extensive remodeling of adjacent tissues to provide a supportive environment for tumor growth, angiogenesis, invasion, and metastasis of cancer cells (Hanahan & Weinberg, 2000; Bissell & Radisky, 2001; Fidler 2002; Chambers et al, 2002)In this chapter we will discuss the role of the microenvironment in the development ofmelanoma. Finally we will discuss the design of in vivo and in vitro models as tools forunderstanding the biology of melanoma as well as their utility for the evaluation of newtreatments.