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Study uncovers molecular keys to invasive bladder cancer
Date:1/29/2014

Seth P. Lerner, M.D., professor and chair of Urologic Oncology and Bladder Cancer program leader at Baylor College of Medicine in Houston.

"We found potential therapeutic targets in 69 percent of tumors and identified bladder cancer subtypes based on gene mutation and expression data," Lerner said. "One subtype looks similar to squamous cell cancer of the head, neck and lung and basal-like breast cancer. Another subtype looks similar to luminal A breast cancer. These genomic similarities create a logical path to test targeted therapies from these other subtypes of cancer rather than treating bladder cancers as one disease."

Lerner said long-term planning for clinical trials based on the TCGA data has begun in earnest and will continue this week during the 2014 Genitourinary Cancers Symposium in San Francisco.

Researchers analyzed tumors for genetic mutations, gene copy number (deletions and amplifications), gene expression of messenger RNA, microRNA and protein expression, among other factors.

Two biological pathways provided the most common therapeutic targets, including molecules addressed by drugs in clinical trials or approved for other types of cancer.

  • 45 percent of tumors had targets in the growth-factor-signaling receptor tyrosine kinase/MAPK pathway, including HER2 best known as a drug target in about one third of breast cancers in 15 percent of tumors, EGFR in 9 percent and FGFR3 in 17 percent.
  • 42 percent had targets in the PI3K/AKT/mTOR pathway, including PIK3CA, which occurred in 17 percent of tumors, TSC1 or TSC2 in 9 percent and AKT3 in 10 percent of tumors. PI3K inhibitors are under development and mTOR inhibitors have been approved for select cancers.

A striking new finding, Weinstein said, was of frequent alterations in genes involved with the regulation of chromatin, the combination of DNA and histone proteins that makes up chromosomes.

Chromatin remodeling greatly influences
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert

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