Researchers unlock personalized cancer medicine with Tumor metabolism

The identification of gene mutations in cancer patients to predict clinical outcome is the cornerstone of cancer research for nearly three decades, but now researchers at the Kimmel Cancer Center at Jefferson, a new approach that instead links cancer cell metabolism with poor clinical outcomes have invented. This approach can now be applied to almost any type of human cancer cell.

The researchers demonstrate that recurrence, metastasis and poor clinical outcome in breast cancer patients by just gene profiling cancer cells that are using ketones and lactate as a food supply can be identified.

These findings have been reported in the April 15, online issue of the cell cycle. The researchers questions this new approach to personalized cancer medicine "Metabolo-genomics."

High-energy metabolites have long suspected is "fuel" aggressive tumor cell behavior. The researchers used this principle to generate a gene expression signature from cancer cells genetically identical, but one cell group was fed a diet of high-energy metabolites. This lactate and ketone-induced "gene signatures" than predicted recurrence, metastasis and poor survival.

So, it seems that what cancer cells eat clinical results, not necessarily new gene mutations.

Michael p. Lisanti, M.D., Ph.d., Professor and Chair of stem cell biology & regenerative medicine at the University of Jefferson Medical College of Thomas Jefferson and a member of the Kimmel Cancer Center at Jefferson, along with other researchers, found that the treatment of human breast cancer cells with high-energy metabolites the expression of genes associated with normal stem cells increases, including genes upregulated in embryonic and neural stem cells.

What's more, lactate and ketones were found to promote the growth of normal cells from stem cells, which critical applications of stem cell transplantation and a host of other diseases in humans. It seems that this increase in metabolites "stemness" cancer cells, what drives worse results.

"That the Tumors of own body nutrients (lactate and ketones) used as" fuel "a worse result for patients survive, a behavior that can now be used to predict as a patient at high risk for recurrence or metastasis is, "said Dr. Lisanti. "This is still the heart of personalized cancer medicine. Now, we have identified a panel of biomarkers that directly links cancer metabolism with targeted cancer therapy. "

These findings suggest, according to the authors, that high risk patients (those whose cancer cells with high-energy metabolites) may be treated with new therapeutics aimed at mitochondrial oxidative metabolism, such as the antioxidant metformin, a drug which is also used for the treatment of diabetes.

Martinez-Outschoorn, M.D., of the Department of medical oncology at the Thomas Jefferson University said "to know the gene signatures of patients whose cancer cells" "these metabolites (lactate and ketones) for fuel is a crucial piece of new information we can use for detecting and treating patients with cancer", and the lead author of the paper. "It's not just that we know that patients will have bad survive; We know that those patients Mitochondrial Metabolism, the type of the energy metabolism of the that we should be focused on with new anti-cancer drugs used. "

The researchers argue that this new approach to diagnosis and treatment of the later "Metabolo-Genomics" be called because it contains both cell metabolism and gene transcriptional profiling. This strategy can now be used to direct where patients receive a certain "tailor-made" anti-metabolic therapy.

Genetic markers, such as expression of the mutationally activated HER2 gene, provided biomarkers that can be used to identify breast cancer patients at high risk for recurrence or metastasis, and until their later treatment with targeted therapies (i.e., herceptin, a drug that is used in aggressive breast cancer) change. But with "Metabolo-Genomics," it is now about the use of "global" cancer cell metabolism of these predictions.

"Just by feeding cancer cells a certain energy-rich diet, changes their character, without mutations introduction or modification of their genetic profile," said Dr. Lisanti. "We only have fed them high energy nutrients that help when using their mitochondria, and this changes their transcriptional profile. It is a new biomarker for "lethal" cancer that we are now with the right drugs, such as the antioxidant metformin treatment can. "

Dr. Lisanti and his colleagues believe that tumor metabolism is the new big picture for the understanding of how cancer undergo repetition and metastasis.

This study was supported by grants from the National Cancer Institute, the Susan g. Komen Breast Cancer Foundation, the Breast Cancer Alliance Countries berger Foundation and a scholar of the American Cancer Society (ACS). This project is also funded, in part under a grant with the Ministry of health of Pennsylvania.

All researchers at Thomas Jefferson University or be connected to the Kimmel Cancer Center and declare no conflict of interest.

Source:
Thomas Jefferson University

Drug-information on Herceptin.