Sunday, January 29, 2017

Phenformin (not metformin) can reduce growth of melanoma cells

For what it's worth:  

Metformin monotherapy in melanoma: A pilot, open-label, prospective and multicentric study indicates no benefit.   Montaudie, Cerezo, Bahadoran, et al.  Pigment Cell Melanoma Res. 2017 Jan 25.

Targeted therapies and immunotherapies have significantly improved the prognosis of patients with advanced melanoma. Unfortunately, treatment failure due to primary and secondary drug resistance are still observed and therefore there is an urgent need to identify new anti-melanoma agents. The oral anti-diabetic drug metformin belongs to the family of biguanides and it is the most widely used antidiabetic drug in the world.  {However, treatment with metformin indicated no benefit.}
Therapeutic potential of the metabolic modulator phenformin in targeting the stem cell compartment in melanoma.   Petrachi, Romagani, Albini, et al. Oncotarget. 2016 Dec 28.

Melanoma is the most dangerous and treatment-resistant skin cancer. Tumor resistance and recurrence are due to the persistence in the patient of aggressive cells with stem cell features, the cancer stem cells (CSC). Recent evidences have shown that CSC display a distinct metabolic profile as compared to tumor bulk population: a promising anti-tumor strategy is therefore to target specific metabolic pathways driving CSC behavior. Biguanides (metformin and phenformin) are anti-diabetic drugs able to perturb cellular metabolism and displaying anti-cancer activity. However, their ability to target the CSC compartment in melanoma is not known. Here we show that phenformin, but not metformin, strongly reduces melanoma cell viability, growth and invasion in both 2D and 3D (spheroids) models. While phenformin decreases melanoma CSC markers expression and the levels of the pro-survival factor MITF, MITF overexpression fails to prevent phenformin effects. Phenformin significantly reduces cell viability in melanoma by targeting both CSC (ALDHhigh) and non-CSC cells and by significantly reducing the number of viable cells in ALDHhigh and ALDHlow-derived spheroids. Consistently, phenformin reduces melanoma cell viability and growth independently from SOX2 levels. Our results show that phenformin is able to affect both CSC and non-CSC melanoma cell viability and growth and suggests its potential use as anti-cancer therapy in melanoma.

Good to know. at a model/cellular level.  Now let's move forward!!! - c

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