"Since its inception in 2006, the ACC Research Program at TGen has made significant strides toward understanding ACC and developing strategies to treat this rare cancer."

Progress to Date

Kirsten’s Legacy is TGen’s premier Adrenocortical Carcinoma (ACC) Research Program and is funding the nation’s most comprehensive genomic study of ACC.

Since its inception in 2006, the ACC Research Program at TGen has made significant strides toward understanding ACC and developing strategies to treat this rare cancer.

The program analyzes ACC tumors, benign tumors and normal tissue by sequencing, or spelling out, the nearly 3 billion chemical letters of each sample. The samples are then compared to discover the mutations, or differences, in the cancer tumors.

Identifying these mutations can help researchers design new diagnostic tests and drug therapies, which could help identify the cancer before it spreads and lead to longer, higher-quality life.

TGen researchers recently completed the first whole genome sequencing of an ACC tumor. By identifying the nearly 3 billion chemicals in the tumor DNA and comparing it to the patient’s normal DNA, scientists can identify mutations that could lead to better treatments. TGen is conducting whole genome sequencing on more ACC tumors and normal tissue samples in an effort to uncover the full complement of each tumor's genetic mutations. TGen is the first in the world to map the entire genome of an ACC tumor.

The development of TGen’s ACC Research Program also led to the establishment by TGen and Scottsdale Healthcare of a joint rare tumor clinic to treat patients.

For example, the Virginia G. Piper Cancer Center (VGPCC) Clinical Trials at Scottsdale Healthcare, a partnership with TGen, is conducting clinical trials for a drug designed to combat ACC. Clinicians hope the new compound, called OSI-906, will stop ACC tumor growth — perhaps even promote tumor shrinkage — without the toxic side effects of current chemotherapies. This study, at one of the nation’s largest ACC trial sites, focuses on patients with inoperable tumors who have relapsed or failed to respond to conventional therapies.

Based on the TGen ACC team’s laboratory tests, other TGen/Scottsdale Healthcare clinical trials are looking at the potential benefits of targeting specific proteins and enzymes associated with ACC with already approved FDA drugs.

As part of the program, TGen houses one of the world’s largest frozen ACC tissue banks. These include dozens of ACC tumor samples, benign adrenal tumor samples, and normal adrenal samples for use in comparisons. These samples eventually will undergo state-of-the-art sequencing.

ACC cell lines and other data sets also are being developed for future research. TGen plans to develop new ACC cell lines that will be used to study potential therapeutic targets.

Current milestones include:

  1. TGen was first in the world to open Phase III, ACC-specific, multi-site clinical trial of OSI-906 at one of the largest ACC sites in the country;

  2. Experimental results from the TGen ACC team resulted in the initiation of Phase I studies of an Eg-5 inhibitor and PLK-1 antagonist;

  3. Developed a valuable bank of relevant tissue samples: 62 ACC tumor samples, 29 benign adrenal tumor samples, and 26 normal adrenal samples;

  4. Generated two messenger RNA (mRNA) expression-profiling data sets, two array CGH data sets, one SNP data set, and one miRNA data set from patient tumor samples;

  5. Generated results led to numerous presentations at the American Association for Cancer Research (AACR), American Society of Clinical Oncology (ASCO) and other national meetings;

  6. Three published papers, with additional ones in press and preparation;

  7. Filed three provisional patents: one for work related to SIRT1 and chemotherapeutic response in ACC; one related to PTTG1 and patent prognosis; and the other for a new process to separate diverse clones within a tumor population for genomic analysis;

  8. Generated sufficient preliminary data to support the award of an institutional research pilot grant funded by the American Cancer Society;

  9. Entered into a sponsored research collaboration with OSI Pharmaceuticals Inc. of Melville, N.Y. to utilize the patient sample repository to further explore potential drug target expression at both the RNA and protein levels to identify new potential therapeutic options for patients; and Led to the establishment of a joint TGen and Scottsdale Healthcare rare tumor clinic to treat patients.