Breast Cancer – Developing Better Chemotherapeutic Agents

Public Health Burden
Over 200,000 new cases of invasive breast cancer are diagnosed in the United States each year, and approximately 40,000 of those diagnosed die from the disease. Breast cancers are routinely classified by stage, pathology, grade, and molecular profiling.

Cancers that do not have any of these molecular markers are called triple-negative breast cancers (TNBC). They account for 15 percent of all globally diagnosed breast cancers and disproportionately affect younger women. TNBC are more likely to recur earlier in places other than breast tissue, and they have a generally poorer prognosis than other breast cancers.

Molecules that block the DNA-marking enzyme histone deacetylase have emerged as a promising new class of cancer drugs. One of these in particular is panobinostat, a powerful blocker of histone deacetylase that can shut down multiple cancer-related pathways and reverse DNA-marking effects that have been linked to cancer progression.

  • This ARRA-supported project demonstrates a potential therapeutic role for panobinostat in targeting aggressive TNBC cell types.4
  • Panobinostat killed TNBC cells in a cell culture model and decreased tumor formation.

Importance to Human Health
This study took place at Tulane University, whose medical center primarily targets an under served, African American population. TNBC disproportionately affects African Americans; the physician-scientist who led this study is an oncologist who regularly treats TNBC in this population in her clinical practice. TNBCs are generally more aggressive and more likely to recur than other types of breast cancer.

Additionally, there are no currently available drug therapies that specifically target TNBC tumors. A great need exists for cancer drugs that can effectively treat TNBCs. Because the results of this project point to the panobinostat’s ability to kill TNBC cells in culture, the researchers want to conduct further studies to determine its potential as a therapy for TNBC. The study team hopes to soon conduct a clinical trial that evaluates the effectiveness of panobinostat in humans with TNBC.

Quotes from the Principal Investigator
This ARRA-funded grant, in addition to enabling this important scientific advance, provided the opportunity for a young physician-scientist to establish herself as an independent researcher under the guidance of a seasoned scientific mentor. “Physician scientists [who are] absolutely committed to research [are] a rapidly dying breed in our system. Dr. Collins-Burrow, who is an MD/PhD, is very dedicated to an academic career…[Due to the time she spent finishing her clinical training], she needed a prolonged ramp-up time to get her own program up to speed again before she could get her own independent funding. The ARRA money…rapidly accelerated her ability to get her lab going and to generate the data she needed to submit an R01. She just submitted an R01 grant that is now under review.”– Prescott L. Deininger, Ph.D

With the ARRA funds, “we’ve developed…a truly translational physician scientist: somebody that’s the hardest thing we can develop in the biomedical enterprise and we’ve helped her take a really big step forward to be able to really stand on her own feet in terms of research… She’s been able to knock out five papers in the last couple of years to reestablish herself as an active researcher again, which is really important when you’re trying to get your grants out.” – Prescott L. Deininger,Ph.D

Contributing NIH Institutes & Centers

  • National Center for Research Resources (NCRR)

  1. Jemal A, et al. Global Cancer Statistics. Cancer J Clin 2011;61: 69-90.
  2. Tate CR, et al. Targeting triple-negative breast cancer cells with the histone deacetylase inhibitor panobinostat. Breast Cancer Res. 2012;14(3):R79.
  3. Deininger, Prescott/Tulane Cancer Center (P20-RR-020152-06S1, Mentoring a Cancer Genetics Program)