Specimen Donations

The entire research endeavor is based upon the support of patients. By consenting to provide tumor specimens, patients jumpstart the entire process of developing biobanks, animal models and cell lines – the building blocks upon which improved therapies may be discovered. Indeed, tumor donations permit patients to take an active role in eventually helping other patients – and perhaps themselves.

The most useful specimens for research are those that are made available to researchers within hours of surgery (fresh or frozen). So it is imperative that patients inform their surgeons ahead of time that they would like to donate for research any excess tumor that won't be required for their own follow-up care.

For more information on how patients may donate tumor specimens, please click here.

Biobanks and Patient Databases

Biobanks are crucial to the research endeavor in two ways. First, they provide the inputs for the gene-based and protein-based studies that are involved in developing targeted therapies and improved diagnostics. Second, if they are combined with patient records, they provide an invaluable resource from which to undertake correlative studies on patient outcomes.

• M.D. Anderson Cancer Center – ACCRF has provided support for a Lab Technician to harvest, process and distribute ACC samples. In addition, pathologic, clinical and follow-up information on ACC cases are maintained.
• University of Virginia – ACCRF has provided support for a Lab Technician to harvest, process and distribute ACC samples. Specimens are banked with available clinical information.
• NIDCR Salivary Gland Tumor Biorepository (SGTB) – Sponsored by the National Institute of Dental and Craniofacial Research (NIDCR) and supported by ACCRF, the SGTB consortium includes six academic medical centers: MD Anderson, the University of Virginia, Johns Hopkins University, the University of Pittsburgh, the University of California, San Francisco and Brown University. Standardized protocols ensure that patients at these institutions may provide their informed consent to donate specimens and help build a shared resource for all researchers with an interest in salivary gland cancers.

Model Development (Cell Lines and Animal Modes)

Cell lines (human tumor cells grown in dishes) are helpful to researchers in understanding the basic biology of a disease as well as for initial screening of drugs. Unfortunately, researchers have found it very difficult to create ACC cell lines. ACCRF is attempting to remedy the situation.

• ACCRF supports the efforts of researchers at the University of Virginia, the Dana-Farber Cancer Institute, the M.D. Anderson Cancer Center, Johns Hopkins University, INCELL, Massachusetts General Hospital and Brigham & Women’s Hospital to grow new ACC cell lines from fresh tumor donations and animal models.
• ACCRF and affiliated investigators collected from labs around the world several cell lines that were purported to be derived from ACC tumors. As the investigators analyzed the cell lines at a molecular level, it became clear that they were derived from non-ACC tumors (see http://www.accrf.org/pdf/accrf_cellupdate_mar09.pdf) As a result, the research community no longer relies upon invalid models for ACC experiments. An affiliated investigator at the University of California, San Fransisco has published on the misidentification issue: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2698276.

Animal models (typically mice with implanted human tumors, called xenografts) help researchers better understand the mechanisms of action, effectiveness, dosing and toxicity of new treatments. In addition, they facilitate the creation of new cell lines.

• ACCRF supports the efforts of researchers at the University of Virginia, the Dana-Farber Cancer Institute, the M.D. Anderson Cancer Center, Massachusetts General Hospital and Johns Hopkins University to create new animal models of ACC. Several xenografts have been created, and more are under development.

ACCRF is committed to making as many models available to researchers as possible. However, it is important that the models are validated and well characterized before they are distributed. Accordingly, ACCRF is working to ensure the quality control of ACC cell lines and xenografts used by affiliated researchers.

Basic Research (Genomics and Proteomics)

Genomics and proteomics involve the study of genes (DNA), RNA and proteins in living cells. Genetic abnormalities are often implicated in the development and progression of cancer. In addition, the RNA and protein products of those genes may be different in tumors than in normal tissues. By identifying the mutated genes, RNA and proteins that are peculiar to ACC, researchers may be able to diagnose patients better and use targeted treatments more effectively.

• DNA Sequencing – ACCRF has a Research Collaboration Agreement with the Wellcome Trust Sanger Institute in the United Kingdom to sequence DNA from ACC  samples. The Sanger Institute was the leading contributor of finished sequence to the Human Genome Project, and its Cancer Genome Project maintains the pre-eminent public database of cancer genes and somatic mutations (http://www.sanger.ac.uk/genetics/CGP/). A pilot ACC sequencing project has identified the somatic mutations in 400 genes across 25 specimens; an extension of the project will sequence all exons (gene regions with the code to make proteins). In addition, paired-end sequencing will identify translocations in the chromosomes of ACC tumors. For more information on the Sanger Institute’s efforts in ACC, please follow this link: http://www.accrf.org/pdf/accrf_spotlight_futreal.pdf. http://www.sanger.ac.uk/genetics/CGP/
• Comparative Genomic Hybridization (CGH) – ACCRF supported the expansion of an array CGH study to identify genetic imbalances and novel target genes in ACC. The study is being conducted at the Sahlgrenska Academy at the University of Gothenburg in Sweden.
• Methylation – ACCRF is facilitating a study of the methylation status of ACC specimens to determine which genes are turned on or off as the disease progresses. The study is being conducted at Johns Hopkins University.
• RNAi – ACCRF has a Research Collaboration Agreement with the Harvard Medical School to identify genes that are essential for the proliferation and/or survival of ACC cells through RNA interference (RNAi) studies. Utilizing short hairpin RNAs (shRNA), researchers will identify potential drug targets to halt or reverse the progression of ACC. For more information on the laboratory conducting the study, please follow this link: http://www.hms.harvard.edu/dms/bbs/fac/harlow.html
• Phosphoproteomics – ACCRF is supporting a study of the phosphorylation status of genes in ACC. By identifying those proteins that are particularly active (rather than merely present), researchers may learn of cell signaling pathways to disrupt in ACC. Cell Signaling Technology is performing the study with the collaboration of the University of Virginia and Massachusetts General Hospital.
• MicroRNA – ACCRF will support studies into microRNAs, cellular molecules whose importance in cancer have become more apparent recently. Depending upon their significance in ACC, micoRNA profiling may indicate additional targets for therapy.
• Bioinformatics – ACCRF will support an open and consistent data platform from which affiliated researchers may analyze the large and growing ACC-specific data sets generated by ACCRF’s basic research projects. In most cases, the same specimens and models have been used in the studies, leading to a particularly rich data set to mine. Computational Biologists at the University of Virginia, MD Anderson and the Sanger Institute will join others in gathering, curating and disseminating data sets from affiliated researchers.

Diagnostic and Prognostic Biomarkers

Biomarkers are biochemical features that can be used to measure the progress of disease or the effects of treatment. ACCRF’s basic research into mechanisms of action in ACC may well uncover biomarkers that will prove helpful in diagnosing patients earlier and guiding treatment for individual patients based on the prognosis indicated by their particular biomarkers.

• ACCRF will support the development of diagnostic and prognostic tests for ACC as appropriate biomarkers are discovered.
• Magnetic Resonance Imaging (MRI) – ACCRF supports researchers at the University of California, Los Angeles in their efforts to study perineural invasion (PNI) in ACC patients with high-resolution MRI. ACC has a peculiar propensity to grow along nerves, so a better understanding of that PNI process may improve the diagnosis, surgical treatment and outcomes for ACC patients.

Drug Screening

Before a new treatment for ACC may reach patients through clinical trials, it must be subjected to rigorous screening for toxicity and efficacy in vitro (in cell lines) and in vivo (in animal models). Screens may be conducted with clinically-relevant drugs (those currently available to patients) or even with libraries that comprise hundreds of thousands of compounds. By correlating the genomic profiles of the cell lines or animal models with their sensitivity to the drugs, researchers may be able to identify subsets of patients for whom treatments are particularly effective.

• Clinically-Relevant Drug Screens – ACCRF is facilitating the provision of ACC cell lines to the Center for Molecular Therapeutics at the Massachusetts General Hospital. Drug screening with approximately 110 clinically-relevant compounds is being carried out on the cell lines, providing information on their sensitivity to drugs and perhaps leading to the optimization of molecularly-targeted therapies for ACC. For more information, please follow this link:http://www2.massgeneral.org/cancer-research/groups.aspx?id=66.
• High-Throughput Screens – ACCRF is collaborating with the NIH Chemical Genomics Center (NCGC) to conduct high-throughput screening (HTS) on ACC cell lines with their library of over 300,000 compounds. Of particular interest will be the 2,000+ FDA-approved compounds as well as the 14,000 compounds with annotated bio-activity. In addition to the prospect of finding promising drugs directly, the project may permit researchers to induce the mechanisms of action in ACC. For more information on the NCGC, please follow this link: http://www.ncgc.nih.gov/
• Xenograft Screening – Drug screening in mouse models typically precedes the movement of novel therapies into clinical trials. ACCRF is consolidating the animal models developed by its affiliated researchers at one institution, South Texas Accelerated Research Therapeutics (START). This program permits cost-effective drug screening that will be made available to all researchers, whether from academic, government or private institutions. The information gleaned from the genomic, proteomic and HTS studies will help researchers decide upon the most promising compounds to screen in the animal models. For more information on START, please follow this link: http://www.startthecure.com/

Clinical Trials

The goal of the Research Agenda is to get effective drugs to patients. Clinical trials are the testing ground for effectiveness and toxicity in humans. They may involve a drug that has already been approved for another cancer or condition, or a novel drug that has yet to receive regulatory approval for any indication.

Clinical trials are particularly difficult to organize for rare conditions such as ACC because multiple clinical institutions must coordinate in order to enroll sufficient patients. It is far simpler to plan the scientific, logistical, regulatory and statistical elements of a clinical trial within one hospital or cooperative group. And private pharmaceutical firms may not be willing to finance the high cost of clinical trials for a small patient population that may not generate much revenue.

• By supporting the generation of data on biological mechanisms of action and pre-clinical drug efficacy, ACCRF is providing rationales for designing ACC-specific clinical trials that are more likely to yield improved therapies. Patients are more likely to enroll in such trials and the NIH and private pharmaceutical firms are more likely to sponsor such clinical trials.
• ACCRF communicates regularly with the medical oncologists at the leading head & neck cancer institutions who treat most ACC patients. These relationships will be crucial as multi-institutional groups are formed to push clinical trials forward for ACC patients.
• ACCRF Co-Founder Marnie Kaufman is serving a 3-year term on the National Cancer Institute’s Head & Neck Steering Committee (HNSC). The HNSC’s role is to prioritize and design large Phase 2 and Phase 3 clinical trials in cancers of the Head and Neck. The 22-member Steering Committee will benefit from the work of four Task Forces: (1) Metastatic/Recurrent Disease, (2) Rare Tumors, (3) Previously-untreated Locally Advanced Disease, and (4) Tumor Biology and Imaging. As a voting member, Marnie Kaufman is well positioned to learn of all new drugs and trials being considered for NCI funding. In addition, she will serve as a bold advocate for clinical trials in under-researched rare tumors like ACC.

ACCRF constantly seeks to improve its Research Agenda and to learn about new avenues of research that might benefit ACC patients. All comments and suggestions are welcome, and may be directed here