Tag Archives: John Carpten

prevention trial - brain scan images

Ivy Foundation Grants Over $9M for Brain Cancer Research

The Ben & Catherine Ivy Foundation (Ivy Foundation) announced its 2012 grant recipients, which total more than $9 million in funding for brain cancer research. The Ivy Foundation is the largest privately funded brain cancer research foundation in North America. Catherine Ivy is the founder and president of the Ivy Foundation, which has a research funding focus on glioblastoma multiforme (GBM), the most common and deadliest of malignant primary brain tumors in adults.

The Ivy Foundation awarded the following grants and/or provided funding in 2012:

· $2,500,000 over three years:  Principal Investigator, Greg D. Foltz, M.D., Director, The Ben & Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Medical Center
· $5,000,000 over five years:  Principal Investigators, John Carpten, Ph.D. and David Craig, Ph.D., Translational Genomics Research Institute (TGen) – a collaborative effort with University of California, San Francisco; University of California, Los Angeles; Memorial Sloan-Kettering Cancer Center; Massachusetts General Hospital; Dana Farber/Harvard Cancer Center; MD Anderson; and University of Utah
· $45,000 annually: Principal Investigator, Brandy Wells, Translational Genomics Research Institute (TGen), for the Ivy Neurological Sciences Internship program
· Over $2 million paid out in 2012 for previously committed multi-year brain cancer research grants

“We are encouraged and remain strongly committed to moving the progress forward for patients diagnosed with brain cancer,” said Ivy. “The 2012 Ivy Foundation grant recipients are important strategic partners in our objective to double the life expectancy of people diagnosed with GBM within the next seven years.”

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TGen-US Oncology data helps triple-negative breast cancer patients

Genomic sequencing has revealed therapeutic drug targets for difficult-to-treat, metastatic triple-negative breast cancer (TNBC), according to an unprecedented study by the Translational Genomic Research Institute (TGen) and US Oncology Research.

The study is published by the journal Molecular Cancer Therapeutics and is currently available online.

By sequencing, or spelling out, the billions of letters contained in the genomes of 14 tumors from ethnically diverse metastatic TNBC patients, TGen and US Oncology Research investigators found recurring significant mutations and other changes in more than a dozen genes. In addition, the investigators identified mutations previously unseen in metastatic TNBC and took the sequencing data into account in selection of therapeutic protocols specific to each patient’s genetic profile.

“This study stands as a one-of-a-kind effort that has already led to potentially beneficial clinical trials, and sets the stage for future investigations,” said Dr. John Carpten, Ph.D., TGen’s Deputy Director of Basic Science and Director of TGen’s Integrated Cancer Genomics Division, and the study’s senior author.

The most frequently mutated gene among the tumors (seven of 14) was the TP53 tumor suppressor, and aberrations were observed in additional tumor suppressor genes including CTNNA1, which was detected in two of six African American patients (who typically have more aggressive and treatment-resistant disease). Alterations were also seen in the ERBB4 gene, known to be involved in mammary-gland maturation during pregnancy and lactation, but not previously linked to metastatic TNBC.

The study included an “outlier analysis,” which assessed expression patterns for each tumor when compared against the other tumors examined in the study. Specific cancer genes overexpressed among tumors in the study’s cohort included: ALK, AR, ARAF, BRAF, FGFR2, GLI1, GLI2, HRAS, HSP90AA1, KRAS, MET, NOTCH2, NOTCH3, and SHH. Significantly underexpressed cancer genes included: BRCA1, BRCA2, CDKN2A, CTNNA1, DKK1, FBXW7, NF1, PTEN, and SFN.

Each tumor was genomically unique, but nine of the 14 contained alterations in one or both of two particular cellular pathways: RAS/RAF/MEK/ERK and PI3K/AKT/MTOR.  Targeted therapeutic intervention aimed at these pathways achieved impressive responses in several cases.

“Importantly, the analysis provided insights into the potential unique therapeutic vulnerabilities of each cancer,” said Dr. Joyce O’Shaughnessy, M.D., the study’s other co-lead author. Dr. O’Shaughnessy is a practicing oncologist with Texas Oncology — an affiliate of The US Oncology Network — and is the Celebrating Women Chair of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center.

Metastatic TNBC is a highly aggressive form of breast cancer that disproportionately affects African-Americans. It is called triple-negative because tumors do not express the estrogen receptor, progesterone receptor or HER-2, the biomarkers successfully targeted in most breast cancers.

Metastatic TNBC also has a poor prognosis once the cancer has spread to other organs, with a median survival rate among metastatic patients of only one year. While TNBC accounts for only about 15 percent of all breast cancers, its more aggressive biology makes it responsible for nearly one in four deaths related to this disease.

“The nature of this disease cries out for innovative research techniques such as whole genome sequencing coupled with new tools for data analysis,” said Dr. David Craig, Ph.D., TGen’s Deputy Director of Bioinformatics, and one of the study’s co-lead authors.

“We are aware that these results are preliminary and based on a small series of patients,” said Carpten. “However, our study will pave the way for new clinical trials and novel hypotheses for future testing in a very difficult to treat cancer.”

Whole-genome sequencing of tumors and normal tissue was performed on Life Technologies Corporation’s Applied Biosystems SOLiD™ 4.0 platform, and results were validated in a CLIA-certified laboratory.

The study, “Genome and transcriptome sequencing in prospective triple negative breast cancer uncovers therapeutic vulnerabilities,” is sponsored by the Translational Genomics Research Institute (TGen) and US Oncology Research with support from Life Technologies Corporation.

Molecular Cancer Therapeutics is one of several peer-reviewed scientific journals published by the 34,000-member American Association for Cancer Research (AACR), the oldest and largest scientific organization in the world focused on every aspect of high-quality, innovative cancer research. The programs and services of the AACR foster the exchange of knowledge and new ideas among scientists dedicated to cancer research, provide training opportunities for the next generation of cancer researchers, and increase public understanding of cancer.