HER2 Support Group Forums - View Single Post - exciting preclinical finding re metformin (diabetes drug) killing cancer stem cell

Rich66 · 05-12-2010, 07:56 AM

The good news is that since it is a widely used prescription drug that a doctor has authority to prescribe off label, more docs will be willing to consider this..as opposed to supplements that they may feel are nonsense.

Regarding what it works on, the most interesting aspect of this (to me) is that it seems to work at a level more fundamental than the overlying subtypes:

Cancer abolishes the tissue-type specific differences in the phenotype of energetic metabolism
Acebo Paloma, Daniel Giner, Piedad Calvo, Blanco-Rivero Amaya, Alvaro D Ortega, Pedro L Fernández, Giovanna Roncador, Fernández-Malavé Edgar, Margarita Chamorro and José M Cuezva
Abstract Full Article
"Unexpectedly, we find that tumors from different tissues and/or histological subtypes have the same cellular content of these markers and, therefore, the same bioenergetic signature. It seems that cancer alters the expression of the markers of energetic metabolism of the cell in a tissue-specific manner (Table 1), consistent with the variable cellular response that oncogenes [3,24,25] and tumor suppressors [2,5,26] have on the phenotype of energetic metabolism. However, it is noteworthy that the bioenergetic signature is basically the same regardless of the tissue of origin and the histological type of the tumor (see β-F1/GAPDH ratio in Table 1 and Figure 2F). These findings could support that a common origin for tumors arises from an undifferentiated progenitor cell and that cancer cells undergo a process of dedifferentiation to acquire the traits of embryonic stem cells[27]. In this regard, we suggest that the bioenergetic signature of the tumors and, hence, the expression of markers of energetic metabolism partially respond to the installment of the reductive metabolic program (mainly glycolytic) that sustains cellular proliferation [15,28]. Conversely, the suppression of the tissue-specific differences in the bioenergetic signature of the tumors and its drastic reduction in certain tissues (Table 1) strongly support that containment of the mitochondrial bioenergetic activity in the cancer cell is an event required for tumor progression. Indeed, tumors with a low bioenergetic signature have a worse prognosis [6–8,10] and the activity of mitochondria has been shown to act as a tumor suppressor [12,14,29].
Owing to the convergence of breast, lung, and esophageal tumors on the same bioenergetic signature, it seems that energetic metabolism affords a common target for cancer therapy. In this regard, several groups and biotech companies are currently targeting the proteins of energetic metabolism as a promising approach to eradicate different types of tumors especially in combined therapy [30–33]. Overall, and because the bioenergetic signature provides a predictive marker of the response of tumors to chemotherapy [9], in agreement with the role of mitochondrial oxidative phosphorylation in the execution of cell death [11,13,14], we suggest that its translation to the clinics will benefit cancer patients."
....
the results support that energetic metabolism represents an additional hallmark of the phenotype of the cancer cell and a promising target for the treatment of diverse neoplasias

05-12-2010, 07:56 AM	#7
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: exciting preclinical finding re metformin (diabetes drug) killing cancer stem cel The good news is that since it is a widely used prescription drug that a doctor has authority to prescribe off label, more docs will be willing to consider this..as opposed to supplements that they may feel are nonsense. Regarding what it works on, the most interesting aspect of this (to me) is that it seems to work at a level more fundamental than the overlying subtypes: Cancer abolishes the tissue-type specific differences in the phenotype of energetic metabolism Acebo Paloma, Daniel Giner, Piedad Calvo, Blanco-Rivero Amaya, Alvaro D Ortega, Pedro L Fernández, Giovanna Roncador, Fernández-Malavé Edgar, Margarita Chamorro and José M Cuezva Abstract Full Article "Unexpectedly, we find that tumors from different tissues and/or histological subtypes have the same cellular content of these markers and, therefore, the same bioenergetic signature. It seems that cancer alters the expression of the markers of energetic metabolism of the cell in a tissue-specific manner (Table 1), consistent with the variable cellular response that oncogenes [3,24,25] and tumor suppressors [2,5,26] have on the phenotype of energetic metabolism. However, it is noteworthy that the bioenergetic signature is basically the same regardless of the tissue of origin and the histological type of the tumor (see β-F1/GAPDH ratio in Table 1 and Figure 2F). These findings could support that a common origin for tumors arises from an undifferentiated progenitor cell and that cancer cells undergo a process of dedifferentiation to acquire the traits of embryonic stem cells[27]. In this regard, we suggest that the bioenergetic signature of the tumors and, hence, the expression of markers of energetic metabolism partially respond to the installment of the reductive metabolic program (mainly glycolytic) that sustains cellular proliferation [15,28]. Conversely, the suppression of the tissue-specific differences in the bioenergetic signature of the tumors and its drastic reduction in certain tissues (Table 1) strongly support that containment of the mitochondrial bioenergetic activity in the cancer cell is an event required for tumor progression. Indeed, tumors with a low bioenergetic signature have a worse prognosis [6–8,10] and the activity of mitochondria has been shown to act as a tumor suppressor [12,14,29]. Owing to the convergence of breast, lung, and esophageal tumors on the same bioenergetic signature, it seems that energetic metabolism affords a common target for cancer therapy. In this regard, several groups and biotech companies are currently targeting the proteins of energetic metabolism as a promising approach to eradicate different types of tumors especially in combined therapy [30–33]. Overall, and because the bioenergetic signature provides a predictive marker of the response of tumors to chemotherapy [9], in agreement with the role of mitochondrial oxidative phosphorylation in the execution of cell death [11,13,14], we suggest that its translation to the clinics will benefit cancer patients." .... the results support that energetic metabolism represents an additional hallmark of the phenotype of the cancer cell and a promising target for the treatment of diverse neoplasias __________________ Mom's treatment history (link)