Researchers unlock, personalized cancer therapy with tumor metabolism

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Identify of mutations du gène in cancer patients to predict clinical outcome is for nearly three decades the cornerstone of cancer research, but now, researchers at the Kimmel Cancer Center at the Jefferson invented a new approach that combines cancer cell metabolism instead with poor clinical outcome. This approach can now be applied to virtually any type of human cancer cell.

The researchers show that simply through recurrence, metastasis and poor clinical outcome in patients with breast cancer gene profiling of cancer cells, which use ketones and lactate can be identified as a food supply.

These findings are reported in the April 15th online edition of the cell cycle. The investigators call for this new approach for personalized cancer medicine "Metabolo Genomics."

High energy metabolites have long "fuel" aggressive tumor cell behavior has been suggested. The researchers this premise used to generate a gene-expression signature of genetically identical cancer cells, but was a House Group fed a diet of high energy metabolites. This lactate and ketone induced "Gene signatures" advance then recurrence, metastasis and poor survive.

It seems that cancer cells are eating what clinical outcome, new mutations du gène determines.

Michael p. Lisanti, m.d., PhD., Professor and Chair of stem cell biology & new planning medicine at Jefferson Medical College of Thomas Jefferson University and member of the Kimmel Cancer Center at Jefferson, found together with other researchers, that the treatment of human breast cancer cells with high energy metabolites increased the expression of genes associated with normal stem cells, including gene Upregulated in embryonic and neural stem cells.

What's more, lactate and ketones to promote the growth of normal stem cells, which has critical applications for stem cell transplant and for a number of different diseases in humans have been found. It seems that these metabolites "Stemness" increase in cancer cells, the drives worse results.

"Tumors that use body's nutrients (lactate and ketones), a worse result for survival, a behavior that can be used now have such as"Fuel"to predict whether a patient at high risk for recurrence or metastasis, is", said Dr. Lisanti. "This is the personalized cancer medicine in the heart." "Now we have identified a panel of biomarkers that directly linked cancer metabolism with targeted cancer therapy."

These findings suggest the authors that high risk cancer patients (those whose Krebszellen use high energy metabolites) with new Therapeutics, target the mitochondrial oxidative metabolism, such as such as the anti-oxidative metformin, a drug, also with the treatment of diabetes, treatment can be.

"To know, for fuel, a central piece of new information, we can use, diagnosis and treatment of cancer patients, is the gene signatures of patients, their Krebszellen these metabolites (lactate and ketones)"are eating"" said Martinez-Outschoorn, m.d., of the Department of medical oncology at Thomas Jefferson University, and lead author of the paper. "It's not just that we know that these patients survive poor;" "We know that those patients use Mitochondrial Metabolism, which is the type of energy metabolism, we should be goals with new anti-cancer drugs."

The researchers propose that this new approach to diagnosis and subsequent treatment "Metabolo Genomics" be called because it contains both cell metabolism and gene transcriptional profiling. This strategy could be used directly the patients get a special "tailor-made" anti-metabolic therapy.

Genetic markers, such as expression of mutationally enabled the HER2 gene, provide biomarkers that can be used to identify patients with breast cancer at high risk for recurrence or metastasis and its subsequent treatment with targeted (i.e., Herceptin, a drug in aggressive breast cancers) change. But with "Metabolo Genomics," it is now on the use of "global" cancer cell metabolism for this prediction.

"Only by the feeding of cancer cells of certain energy-rich diet, it changes its character, mutations without introduction or change their genetic profile," said Dr. Lisanti. "We only have it fed high energy nutrients that help them use their mitochondria, and this changes their transcriptional profile." "It is a new biomarker for"lethal"types of cancer, we can now handle with the right medications, such as for example the antioxidant metformin."

Dr. Lisanti and his colleagues believe that the tumor metabolism is the new big picture for understanding how cancer recurrence and metastasis are subjected.

This study was conducted through grants from the National Cancer Institute, the Susan G. Komen Breast Cancer Foundation, the Breast Cancer Alliance, shopping's Foundation and a scholar research supported by the American Cancer Society (ACS). This project is also partially funded under a grant with the Pennsylvania Department of health.

Declare all researchers at Thomas Jefferson University with the Kimmel are connected Cancer Center and no conflicts of interest.

Source:
Thomas Jefferson University

See drug information on Herceptin.