Introduction

Melanoma Resistance: A Bright Future for Academicians and a Challenge for Patient Advocates

“…Melanoma cells also have the capability to produce corticosterone and cortisol, a property shared by normal melanocytes and other skin cells (as previously reviewed by Slominski et al 17 ). Interestingly, this production can be stimulated by locally expressed corticotropin-releasing factor (CRF) and POMC-derived ACTH (as previously reviewed by Slominski et al 18 ).…”

“…This hypothalamic-pituitary-adrenal (HPA)–like axis operates in the skin to attenuate damage imposed by environmental factors and to prevent autoimmune attack against the skin due to damage-induced exposure of cutaneous antigens. 17,18 The misplaced or deregulated HPA-like organization or its elements can also operate under pathologic conditions, such as melanoma, to generate an immunosuppressive and protumor environment that, in turn, facilitates melanoma growth and progression. 18 …”

“…Although the previously mentioned neuroendocrine regulatory pathways are operating on the local, skin, and melanoma levels, 17,18 there also is a strong possibility for concomitant systemic immunosuppressive activity. Specifically, melanoma-derived CRF or CRF-like peptides, interleukin-1, IL-6, tumor necrosis factor α, and ACTH could either activate the pituitary-adrenal axis or directly affect the adrenal cortex, leading to systemic immunosuppression.…”

“…12 Noteworthy, melanoma cells can produce and metabolize catecholamines, serotonin, melatonin, and hormones of the hypothalamic-pituitary-thyroid axis, as well as a variety of other neurotransmitters. 9,11,12,17 Thus, melanomas are empowered with a variety of stress mediators and hormones through which they can control local and systemic immune responses. The corresponding panel of receptors 12 and metabolizing enzymes, cytochromes especially, 19 will facilitate tumor plasticity and survival in response to changes in their environment.…”

Investigation of bioactive compounds with anti-cancer potential in Carica papaya leaves

“…they do not require gastrointestinal absorption for the cells to be exposed to bioactive compounds. Moreover, squamous cell carcinoma, together with basal cell carcinoma, are the most frequent environmentally induced cancers, with UV light being recognized as a key etiologic factor (Slominski et al, 2012, Leiter et al, 2013, Slominski et al, 2014a, Slominski et al, 2014b, Xiang et al, 2014, which is a significant issue in Australia. Research into the development of new therapeutic agents is of considerable importance and attention has recently focused on natural products.…”