If anything, the most reasonable way to spend money is to donate it to scientific research in aging, cancer and age-related diseases. The reason is because the positive effect of those experiments will be useful for everybody, and what the heck, may save the donors life. Id like to introduce the third project on LabCures platform and call for everyone to to donate $25, if not more. Heres what Dr. Benzs lab is going to do: 1. DEVELOPING NEW BREAST CANCER THERAPEUTICS: 1.1. Accelerating decay of HER2 and other oncogenic transcripts. Several of the lab’s most recent publications focus on the polysomal impact of histone deacetylase (HDAC) inhibitors, which they first identified as inducing rapid decay of HER2 and ~300 other oncogenic transcripts, while remaining attached to the polysome translational machinery. By defining the specific ribosomal and transcript binding proteins mediating this novel HDAC-regulated transcript stabilizing mechanism, they can develop more effective therapies against the most aggressive forms of breast and other cancers. 1.2. Decoding ER phosphorylation to develop more effective endocrine therapy. Following their recent mass spec identification of several new ER protein phosphorylation sites, the research group is now focusing on the critical role for ligand induction of ERSer294 phosphorylation via CDK1/2 and its associated factors (cyclins), introducing the possible use of CDK1/2 inhibitors for the treatment of those ER-positive breast cancers that become resistant to various ligand-based therapeutics (e.g. antiestrogens, aromatase inhibitors) because of acquired mutations in their ER ligand-binding domain. 1.3. Inhibiting cancer metabolism and mitochondrial function. Understanding that a hallmark feature of cancer is its need to reprogram cellular metabolism and mitochondrial function (e.g. Warburg effect) to support its energy and biosynthetic requirements, they have now identified and are therapeutically targeting a newly identified mitochondrial energy-producing survival mechanism based on proline catabolism, proline dehydrogenase (PRODH), regulated by the p53 tumor suppressor and coordinated with the known “glutamine addiction” of many breast and other cancers. 2. PREDICTING BREAST CANCER RISK AND IDENTIFYING DRUGGABLE NEW PATHWAYS DRIVING CANCER: 2.1. Clinically validating a new TNBC gene signature, the Integrated Cytokine Score. This 5-gene indicator of good prognosis that could save patients the need for toxic chemotherapy and point to a more beneficial immunotherapy option is now being validated in collaboration with UCSF and Swedish clinical collaborators. 2.2. Establishing a pipeline approach that integrates “omic” data to identify cancer-driving pathways. In partnership with UCSC computer scientists/bioinformaticians and serving the national Cancer Genome Atlas (TCGA) program, they are identifying pathways shared by diverse cancer types to enable the “repurposing” of approved anticancer agents, and discovering new cancer pathways in need of drug development and targeting. 3. COMMUNITY-BASED RESEARCH ON A HIGH-RISK POPULATION TO DESIGN A NEW PREVENTION APPROACH: While the increasing worldwide incidence of ER+ breast cancer has been linked to aging, it is also most pronounced in selected geographic and ethnic populations, including Caucasian women over age 40 who live in Marin County, which is among the world’s highest breast cancer incidence populations. Following their 2002 Buck-sponsored scientific symposium addressing this local issue, they partnered with Marin County (MCDHHS) epidemiologists to initiate the Marin Women’s Study (MWS) in 2006, that has now surveyed >14,000 Marin women at the time of their screening mammogram and collected >8,000 saliva samples, cryobanked at the Buck after Benz lab processing into DNA and solute fractions. Along with MCDHHS, they have published several key findings about this high incidence population, the most recent being their novel discovery that women who experience hypertension during pregnancy (~8% of all pregnant women), and who carry a specific polymorphic (SNP) variant of the IGF1R gene, are protected from developing denser breasts later in life and also from developing breast cancer decades later. The lab has since developed a novel biological hypothesis to explain this key epidemiologic observation, and now has in hand a detailed project plan entitled, “Pregnancy induced hypertension, IGF1R, and breast cancer prevention.” This project will not only validate our Marin County observation across the entire state of California but also use normal breast biopsy samples from around the country (Komen Tissue Bank) to prove our mechanistic hypothesis and generate the necessary rationale to launch an entirely new breast cancer prevention strategy.
Posted on: Tue, 09 Sep 2014 16:10:22 +0000
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