To accomplish this, TGen researchers employ the latest in genomic technologies to analyze ACC tissue, donated through the generosity of patients and collected by research collaborators. TGen’s ACC research team seeks to identify potential targets (genetic markers known to have a positive response to therapeutics) previously not associated with ACC.
In addition to finding more effective diagnostic tools and better treatments, TGen strives to educate clinicians and researchers in the latest findings from the worldwide ACC research community, providing patients with the best care and carrying forward the cancer research baton.
Because ACC is rare, scientific inquiries requiring large sample sets are not possible. With the advent of improved technologies, however, we are now capable of achieving a depth of knowledge of ACC tumor biology previously not possible. These technologies offer the potential to analyze DNA changes and the expression changes of thousands of genes in human tumor tissue. Increased disease-specific genetic knowledge leads to the identification of novel targets to known drugs, while also providing basic knowledge of how the cancer processes develops and evolves in regards to ACC. Understanding these mechanisms will ultimately lead to new and improved prognostic biomarkers and identify new targets for better treatment strategies.
Using the Latest in Genomic Technology
Bringing to bear the latest in biomedical technologies coupled with decades of experience in cancer biology and treatment, TGen scientists plan to help conquer ACC by performing what arguably would be the most in-depth study of ACC tumors ever attempted.
TGen’s ACC Research Program is among a small number of groups worldwide that have the infrastructure and expertise to successfully conduct this study. We are among the first to undertake the ambitious initiative to comprehensively examine the genomes of ACC tumors through multiple techniques, including sequencing the entire genomes of these tumors. We previously have generated what are considered the world’s best characterized set of ACC patient samples, resulting in two Phase I trials of compounds targeting either the MDM2 or Eg5 gene products, as well as a Phase III study of an inhibitor of IGF1R. It is this strong connection between the laboratory and clinic that distinguishes our program from others.
As a community, we have witnessed how increased funding of breast cancer research, both through private and public sources, led to the discovery that it is more than one disease. This in turn has led to more effective treatment for women with this complex disease and a corresponding increased survival, such that the five-year survival rate for breast cancer caught in its earliest stages is now 98 percent.
We believe a similarly aggressive initiative to thoroughly study ACC (another significant goal of Kirsten's Legacy) will result in improved management and breakthrough treatments, giving hope to those who suffer from this deadly cancer.
About The Study
We have designed a comprehensive whole genome sequencing study to profile tumors from patients and their matched normal tissue samples in an unprecedented way, uncovering the full complement of genetic changes within these tumors. We will conduct whole transcriptome sequencing in these samples, plus additional ACCs, normal adrenals, and benign adrenal adenomas. The transcriptome is the set of all RNA molecules produced in one or a collections of cells.
In addition, we will profile tumors not already analyzed previously using the technology employed in the past three years, so all tumors in our repository will have data for all methods of profiling. To establish a much-needed community resource for the in vitro and in vivo study of ACC, we also propose to develop new ACC cell lines. Finally, we will establish a post-doctoral training program for Ph.D.s and M.D.s to further expand the number of researchers and clinicians with a specific interest and expertise in ACC.
With this genomics project, we were the first to attempt and complete the mapping of an entire ACC tumor genome. By sequencing ACC tumor genomes along with their matched normal tissue, as well as performing sequence-based transcriptome profiling on additional tumors, plus normal adrenals and benign adenomas, we will have the most in-depth view of the ACC genome. Any change in the patient tumor cells, relative to their normal cells, will represent potential biomarkers of disease aggressiveness, or stage, or targets for new and better treatment strategies. Simultaneously, we will have generated and characterized cell line model systems for the further validation and study of therapeutic targets in ACC, and expanded the number of experts in ACC research and disease management.
