University of Alabama at Birmingham Research Team Uncovers Elevated Protein Levels in Certain Types of Breast Cancers

-80 degrees freezer ultra lowAcross the United States, biobanks are becoming an increasingly popular resource for scientists studying a wide variety of different conditions. While 17% of these facilities have been in existence for over 20 years, as many as two-thirds were established within the last decade by pharmaceutical companies, universities and everything in between. These centers are a key tool in the practice of translational research, in which findings are directly “translated” into new treatments, therapies and more. Now, one of these studies may have made a significant discovery about a common subtype of breast cancer, which could help lead to more effective, personalized treatments for this common disease.

More than 230,000 women are diagnosed with breast cancer in the United States every year. However, each of these cases is more unique than that statistic would suggest: there are five subtypes of breast cancer, each with distinct biologies that drastically alter their progression and responses to treatment. As a result, understanding the differences between them is an important step in creating effective therapies for patients.

This was the goal of a research team at the University of Alabama at Birmingham, which recently uncovered a key component about one form of breast cancer. Building on previous studies which showed that several types of breast cancers have elevated levels of a DNA repair enzyme called PARP 1, the researchers decided to turn this focus on a subtype called HER2-enriched or HER2+. They began by obtaining preliminary data through the Cancer Genome Atlas, a research program run through the National Institutes of Health (NIH), which is designed to characterize the genomic substructure of different cancers. Then they acquired and studied 307 HER2+ basal or luminal breast cancer tissue samples taken between 1999 and 2012. The samples were stored by the Minority Biospecimen/Biobanking Geographic Management Program, also operated by the NIH.

In a paper titled “PARP1 and phospho-p65 protein expression is increased in HER2-positive breast cancers,” which was published in the journal Breast Cancer Research and Treatment, the researchers reported that they found HER2-enriched or HER2+ breast cancers have elevated expressions of two proteins: PARP1 and phospho-p65. While PARP1 is a DNA repair enzyme, phospho-p65 (also called NF-kB) controls the transcription of DNA and has been previously linked to autoimmune diseases, viral infections and septic shock. Over the course of the study, the team not only proved that PARP1 was prevalent in basal subtype breast cancers, but that HER2+ tumors had higher levels of the two substances than HER2- tumors. Moreover, PARP1 and phospho-p65 were coordinately expressed.

The high PARP1 levels further supports evidence which suggests that certain types of breast cancers may benefit from a type of drug called PARP inhibitors. Meanwhile, NF-kB appears to correlate with tumor aggressiveness, which could explain why HER2+ breast cancer has a fairly poor prognosis. The research team has pointed out that several different companies are testing PARP inhibitors in clinical trials, and one has already been approved to treat advanced ovarian cancer. In light of their findings, they are recommending further research to determine if elevated PARP 1 and phospho-p65 levels can serve as a marker of PARP inhibitor sensitivity, potentially determining additional uses for the medication.

The paper “PARP1 and phospho-p65 protein expression is increased in HER2-positive breast cancers” was co-authored by several researchers from the UAB School of Medicine, including Eddy S. Yang, M.D., Ph.D.; Jennifer Stanley; Lisa Klepczyk, M.D.; Kimberly Keene, M.D.; Monica Wielgos; Shi Wei, M.D., Ph.D.; William Grizzle, M.D., Ph.D.; Jason Brazelton, M.D.; Yufeng Li, Ph.D.; Andres Forero, M.D.; and Albert F. LoBuglio, M.D. Their specialties span several disciplines from oncology to radiology and preventative medicine.

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