Creative Minds: Engineering Targeted Breast Cancer Treatments

Posted on July 8th, 2014 by Dr. Francis Collins

A few years ago, Debra Auguste, a chemical engineer then at Harvard University, was examining the statistics on breast cancer: the second most common cancer in women in the U.S. after lung cancer. She was disturbed to discover that of all the ethnic groups, African American women with breast cancer suffered the highest mortality rates—with 30.8% dying from the disease [1-3].

As an African American woman, Auguste was stunned by this correlation. She wondered whether there was some genetic aspect of breast cancer cells in African Americans that made these cancers more aggressive and more difficult to cure.

To explore the issue, she decided to identify, and map, the arrangement of proteins on the surface of metastatic breast cancer cells from four different groups: African Americans, Caucasians, women under 40, and women over 40. Auguste, now at the City College of New York, believes that if she can identify signature constellations of cell surface proteins, she’ll be able to draw on her engineering background to design drug delivery vehicles that recognize two or more signature proteins and deliver drugs that prevent these cancers from spreading to other organs (called metastasis). We’ve awarded her a 2012 New Innovator Award to test her strategy.

Before I tell you more about Auguste’s approach, let me backtrack to explain that, when it comes to breast cancer, there are already several personalized therapies. One way to classify breast cancers is by the presence or absence of certain proteins on the surface of the cell. Breast cancer cells that are estrogen positive—carrying the estrogen receptor on the surface—grow and proliferate when exposed to the hormone estrogen. Others are progesterone positive; these carry the progesterone receptor and grow and multiply in response to the hormone progesterone. Then, there are cancers that produce too much of the protein called human epidermal growth factor receptor 2 (HER2). These HER2 positive breast cancers are significantly more aggressive, but respond to the monoclonal antibody therapy called Herceptin. Cancer cells with all three proteins are triple positive; those lacking all three are triple negative. Triple negative breast cancers are more common in African American women.

For all of these types except the triple negative, there are specific therapies that can slow tumor growth. Auguste is interested in the treatment-resistant, triple negative cancers. She wants to identify a group of proteins on these cancers that delivery vehicles can use as anchors while they unload their therapy. Auguste has already shown, in vitro, that the delivery vehicles can adhere more tightly to the target breast cancer cell when there are two target proteins rather than just one. With a tighter grip on the cancer, the therapeutic molecules can be precisely delivered.

Together with her collaborator Marsha Moses [4], Andrus Professor at Harvard Medical School and Director of the Vascular Biology Program at Boston Children’s Hospital in Massachusetts, Auguste intends to use multiple antibodies to recognize triple negative breast cancer cells and then deliver molecules that block metastasis. If her approach is successful, we may have a new way to deliver drugs with precision: not just to cancer cells, but to any type of diseased cell or organ with a distinctive pattern of proteins on the surface.

References:

[1] SEER Stat Fact Sheets: Breast Cancer

[2] Population differences in breast cancer: survey in indigenous African women reveals over-representation of triple-negative breast cancer. Huo D, Ikpatt F, Khramtsov A, Dangou JM, Nanda R, Dignam J, Zhang B, Grushko T, Zhang C, Oluwasola O, Malaka D, Malami S, Odetunde A, Adeoye AO, Iyare F, Falusi A, Perou CM, Olopade OI. J Clin Oncol. 2009 Sep 20;27(27):4515-21.

[3] Racial differences in survival from breast cancer. Results of the National Cancer Institute Black/White Cancer Survival Study. Eley JW, Hill HA, Chen VW, Austin DF, Wesley MN, Muss HB, Greenberg RS, Coates RJ, Correa P, Redmond CK, et al. JAMA. 1994 Sep 28;272(12):947-54.

[4] Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade. Guo P, You JO, Yang J, Jia D, Moses MA, Auguste DT. Mol Pharm. 2014 Feb 12.

Links:

The Common Fund. (NIH)

NIH Director’s New Innovator Award

2012 NIH New Innovator Award Recipients

Debra Auguste,The City College of New York, Personalized therapeutics for inhibiting breast cancer metastasis

Auguste Lab, The City College of New York, NY

Marsha Moses, Harvard Medical School, Boston, MA

National Cancer Institute: Breast Cancer

NIH support: Common Fund; National Cancer Institute