PARP Inhibitors Plus EGFR May Slow TNBC Growth

Researchers have successfully slowed the growth of triple-negative breast cancer tumors in lab research that combined PARP inhibitors with EGRF inhibitors.  In the past PARP, or Poly (ADP-ribose) polymerase, inhibitors  have shown mixed results for TNBC.  The difference here might be the effects of EGFR (epidermal growth factor receptor).   The  research was published in PLOS One (The Public Library of Science).  In the summary to the article, the researchers, note,  "Our intriguing and novel results point to the potential broader utility of PARP inhibitors in breast cancer beyond hereditary BRCA1-and BRCA2-deficient tumors by combining it with EGFR inhibitors such as lapatinib. Moreover, the discovery of the novel EGFR-BRCA1 interaction may lead to other therapeutic targets for the highly aggressive TNBC."

The full release, with my inevitable editorial comments about language:

Researchers at the University of Alabama at Birmingham (UAB) reported new discoveries that can slow the growth and metastasis of triple negative breast cancer in the peer reviewed open access journal Public Library of Science on October 11, 2011. Triple negative breast cancer is one of the most lethal forms of breast cancer due to a high rate of spread by metastasis. [NOTE:  IT CAN BE LETHAL BUT IS NOT ALWAYS. MOST WOMEN SURVIVE. WHY DO I HAVE TO REPEAT THIS OVER AND OVER AND OVER?]

The researchers reported a slowed rate of growth of triple negative breast cancer both in the breast and in metastasized tissues by using ABT-888 and lapatinib. Both drugs are known as Poly (ADP-ribose) polymerase (PARP) and act to repair breaks in DNA and also function in programmed cell death.

Combined EGFR and PARP inhibition delays the growth of orthotopic breast tumor xenografts in mice.Photo credit:  doi:10.1371/journal.pone.0046614.g007 Yang et. al. open access

The scientists found that the PARP drugs combine with EGFR (epidermal growth factor receptor) to produce cancer cell death both in the affected breast and metastasized tissues.

Breast cancer type 1 susceptibility protein (BRCA1) and EGFR were found to exist in the same protein complex for the first time. The researchers conclude that this factor is one of the major contributors to the susceptibility of triple negative breast cancer to PARP type drugs.

The scientists also found that cancer reduction through cancer cell death was not dependent on the concentration of EGFR but did require this factor's presence.

The study also suggests that there are six distinct groups of triple negative breast cancers based on gene expression profiles: basal-like 1, basal-like 2, immunomodulatory, mesenchymal, mesenchymal stem-like, and luminal androgen receptor.

All types of triple negative breast cancer are susceptible to the synthetic cancer cell death methodology developed at UAB.

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