Recipients &
Updates from the Lab
NANCY OWENS MEMORIAL FOUNDATION 2011 luncheon proceeds were split between:
Houston Affiliate of Susan G. Komen for the Cure
Lester and Sue Smith Breast Center - Baylor College of Medicine
Updates from the Lab
July 30, 2011
To: The Nancy Owens Memorial Foundation:
Moving towards personalized medicine:
A new technology for rapidly discovering breast cancer therapies
More than 40,000 women will lose their fight with breast cancer this year, underlining the urgent need for new treatments. A major bottleneck in developing new treatments is the slow pace in identifying effective drug targets. We need new, creative strategies for rapidly discovering the key vulnerabilities of human breast cancer.
Ironically, a major barrier to identifying treatments stems from the very nature of how we approach the problem. The vast majority of resources are focused on individuals examining one gene at a time. An investigator implicates a gene in cancer and studies its function in the hope that such an in depth study may lead to a novel treatment. This model has served scientists well for elucidating many biological pathways and is responsible for current progress in cancer biology. However, this discovery model is ill-suited for rapid development of treatments. It assumes that we will eventually stumble on the correct drug target protein using reason and a series of educated guesses. The genome has thousands of unknown proteins and who is to know the correct set of proteins that unlock the key to cancer therapies?
The major goal for any cancer therapy is to selectively kill tumor cells without detrimental effects on a person’s normal cells and tissues. Implicit in this goal is the challenge that therapies must target vulnerabilities unique to cancer cells. Our group has developed a strategy that may fundamentally change the speed in which new anti-cancer targets are discovered. This strategy is based on combining team-oriented science with a novel technology that we recently developed. Unlike traditional “one-gene-at-a-time” approaches, this new technology (termed “RNA interference library”) enables us to rapidly test the functional role of all genes in human cancers.
Using our new technology, we are discovering the genes that breast cancer cells depend on for their aggressive behavior, but are not required by normal cells. In our pilot studies, we have already identified examples of such genes, and demonstrated that inhibiting these genes severely impairs breast cancer progression in animal models. This exciting finding suggests that an entire class of these “breast cancer vulnerabilities” awaits discovery.
With the generous support of the Nancy Owens Memorial Foundation, we have pursued this new class of breast cancer vulnerabilities and have made three major discoveries that will have profound impact on breast cancer research and (more importantly) the treatment of breast cancer patients:
(1) we have expanded our search for these new genes that are “breast cancer vulnerabilities,” and identified over 100 new targets for developing breast cancer therapies.
(2) we have validated that several of these targets can predict which women have “aggressive” (i.e. much more likely to recur).
(3) most excitingly, our research led to the unexpected discovery that 2 FDA-approved drugs, when combined, have profound effects on breast cancers. Each of these drugs alone does not have much effect on breast cancer, and no one has ever thought to put them together. We have shown that the combination of these treatments leads to dramatic regression of tumors (in animal models), AND are now developing a clinical trial based on these discoveries!
In summary, the generous support from the Nancy Owens Memorial Foundation has yielded substantive scientific progress. This progress has culminated in recognition for our research endeavors, and requests to present these discoveries at prestigious venues including a invited platform presentation at the 102nd Annual Conference for the American Association for Cancer Research (AACR). In addition, because of the broad and potentially far-reaching ramifications of our discoveries, this work is being considered for publication in a top-tier journal (Science). Lastly, the potential utility of our technology and approach has led to requests from 2 major pharmaceutical companies for collaborative efforts in the cancer arena, and the development of a new clinical trial based on the combination of 2 FDA-approved drugs.
We want to thank you for your generous support and willingness to support high-risk / high-impact ideas. It is your innovative spirit that has made the discoveries above possible, and is leading towards making a profound impact on breast cancer survivors.
Sincerely,
Thomas F. Westbrook, Ph.D.
Assistant Professor
Department of Biochemistry and Molecular Biology
Department of Molecular and Human Genetics
Baylor College of Medicine
2010 - Trey Westbrook
Using our new genetic technology, we are discovering the genes that breast cancer cells depend on for their aggressive behavior, but are not required by normal cells. In our pilot studies, we have already identified examples of such genes, and demonstrated that inhibiting these genes severely impairs breast cancer progression in animal models. This exciting finding suggests that an entire class of “breast cancer vulnerabilities” awaits discovery.
With the generous support of the Nancy Owens Memorial Foundation, we have pursued this new class of breast cancer vulnerabilities and have made three major discoveries that will have profound impact on breast cancer research and (more importantly) the treatment of breast cancer patients.
2009 - Yi Li
Herceptin is a powerful therapeutic drug for breast cancer, but many patients develop resistance quickly. Treating Herceptin-resistant tumors has been very difficult. With the generous support of the Nancy Owens Memorial Foundation, and in close collaboration with the laboratory of Dr. Rebekah Drezek at Rice University, we completed the engineering and testing of nanoparticles that can selectively bind breast cancer cells that are resistant to Herceptin therapy. This finding has been published in the journal Breast Cancer Research and Treatment. The next goal will be to test whether these nanoparticles can bind Herceptin-resistant tumor cells in mice and can mediate thermal destruction of these tumors.
2008 – Steffi Oesterreich
The Nancy Owens Memorial Foundation allowed us to study how estrogen represses the expression of some target genes in breast cancer. We discovered that the estrogen receptor interacts with a specfic histone deacetylase, termed HDAC7, to repress many of its target genes. Interestingly, many of these genes are tumor suppressors or involved cell death, suggesting that this process could be critical in estrogen-mediated tumor growth. We are currently testing whether targeting HDAC7 could be a novel therapeutic approach for endocrine treatment resistant breast cancer.
2007 – Adrian Lee
A new therapy targeting a growth factor receptor IGF-IR, which is similar to HER2, has recently entered clinical trials. However, at the moment we don’t know which patients should receive this therapy. With the support of the Nancy Owens Memorial Foundation we identified biomarkers of response to anti-IGF-IR therapy and found that this therapy is most active in triple-negative breast cancer cell lines. Importantly, treatment of a human triple negative breast cancer grown in the mouse with both anti-IGF-IR therapy and chemotherapy resulted in complete regression of the tumor. We now continue these studies to determine whether anti-IGF-IR therapy is a new useful tool it the treatment of triple-negative breast cancer.
2006 – Suzanne Fuqua
With the support of the Nancy Owens Memorial Foundation, our lab found a gene called Ebp50 that can cause resistance to antiestrogens like tamoxifen in ER+ tumors or resistance to trastuzumab in HER2+ tumors when it malfunctions in breast cancer. Now we are seeking ways of preventing the development of resistance in these tumors.