Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma

Abstract

Melanoma is a form of cancer that initiates in melanocytes. Melanoma has multiple phenotypically distinct subpopulation of cells, some of them have embryonic like plasticity which are involved in self-renewal, tumor initiation, metastasis and progression and provide reservoir of therapeutically resistant cells. Cancer stem cells (CSCs) can be identified and characterized based on various unique cell surface and intracellular markers. CSCs exhibit different molecular pattern with respect to non-CSCs. They maintain their stemness and chemoresistant features through specific signaling cascades. CSCs are weak in immunogenicity and act as immunosupressor in the host system. Melanoma treatment becomes difficult and survival is greatly reduced when the patient develop metastasis. Standard conventional oncology treatments such as chemotherapy, radiotherapy and surgical resection are only responsible for shrinking the bulk of the tumor mass and tumor tends to relapse. Thus, targeting CSCs and their microenvironment niche addresses the alternative of traditional cancer therapy. Combined use of CSCs targeted and traditional therapies may kill the bulk tumor and CSCs and offer a promising therapeutic strategy for the management of melanoma.

Notch1-MAPK Signaling Axis is Essential in CD133+ Melanoma Initiating Cells

“…Our in vitro and in vivo data showed that CD133 + subpopulation exhibits EMT, metastasis and angiogenesis in melanoma. Previous studies showed that acquisition of chemoresistant is associated with high expression of multidrug resistant (MDR) protein, IL-8 and VEGF [3,8,9]. Our data indicates that CD133 + subpopulation exhibits higher percentage of SP phenotypes which probably associated with chemoresistance against DTIC, Dox, Dabrafenib and Trametinib [7].…”

“…Several reports showed that CD133, CD20, CD271, ABCG2 and ABCB5 act as a potential marker to characterize CSCs in melanoma [3,4]. However, the molecular mechanism between cancer stem cells markers and with their associated functions remains to be elucidated.…”

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

“…Another ABC transporter playing a vital role in malignant skin cancer progression is ABCB5 that is used to identify melanoma stem cells (MSCs). MSCs, called also malignant melanoma-initiating cells (MMICs), belong to the aforementioned subpopulation of malignant cells that are capable of self-renewal and as a consequence lead to cancer development [60,61]. Recent studies show [62].…”

Nanomedicine in Melanoma: Current Trends and Future Perspectives

“…Hence, nanoparticles of biodegradable photoluminescent poly (lactic acid) were loaded with a drug specific for anti-BRAF V600E mutant melanoma forming a complex engulfed further by macrophages which would directly bind and kill melanoma tumor cells (147)(148)(149)(150).…”