• Project Descriptions

    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.

    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 essential inputs for genomic studies that discover diagnostic, prognostic and therapeutic biomarkers. Second, if combined with patient records, they provide an invaluable resource from which to undertake correlative studies on patient outcomes.

    ACCRF has supported both M.D. Anderson and the University of Virginia with funds for Lab Technicians to harvest, process and distribute ACC samples. These biobanking efforts later flourished with the guidance and support of the National Institute of Dental and Craniofacial Research (NIDCR). An additional six academic medical centers joined forces to create the Salivary Gland Tumor Biorepository (SGTB), a shared resource for researchers around the globe with an interest in salivary gland cancers.

    Model Development (Cell Lines and Animal Models)

    Cell lines (human tumor cells grown in dishes) are helpful to researchers in understanding the basic biology of a disease as well as for the initial screening of drugs. Unfortunately, researchers have found it very difficult to create ACC cell lines. The few cell lines that were purported to have been derived from ACC tumors have been found to be cross-contaminated, making them invalid models. ACCRF has supported several institutions trying varied approaches to cell line development and will facilitate the sharing of the resources when successfully developed.

    Patient-derived xenografts are mouse models with implanted human tumors. They help researchers better understand the mechanisms of action, effectiveness, dosing and toxicity of new drugs. In addition, they provide plentiful fresh tumor for genomic studies and may facilitate the creation of new cell lines. ACCRF has supported a few institutions to develop xenografts, with the University of Virginia having been the most successful with nearly 20 models created.

    Transgenic mouse models involve the alteration and control of specific genes to understand tumor initiation and progression. They also may be very useful in screening drugs. ACCRF has supported efforts at the Dana-Farber Cancer Institute and the University of Virginia to develop such models, while NIDCR is supporting another effort at the M.D. Anderson.

    ACCRF is committed to making as many models available to researchers as soon 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 mouse models used by affiliated researchers.

    For more information on ACC cell lines and patient-derived xenografts, see Specimens and Models.

    Basic Research (Biomarker Identification and Validation)

    Cancer is a genetic disease. However, there are many different types of genetic alterations that may lead to cancer and the complexity is daunting. Fortunately, technological advances are permitting high-throughput analysis of many of these genetic alterations at a reasonable cost. It is crucial to identify the genetic alterations and their mechanisms of action in order to understand how to recognize, predict and interfere with the disease process.

    ACCRF has supported an extensive set of genomic studies on the same ACC specimens, developing a data set for a rare cancer that is paralleled by very few common cancers. The studies have included exome sequencing, comparative genomic hybridization, methylation, ChIP-sequencing, gene expression, RNA interference and phosphoproteomics. The institutions involved include the Wellcome Trust Sanger Institute, M.D. Anderson, the University of Virginia, Massachusetts General Hospital, the Sahlgrenska Institute, Cell Signaling Technology and Johns Hopkins, among others.

    There is substantial value in each stand-alone data set. However, the integration of the data sets generated from various platforms within one bioinformatics effort should yield additional, powerful insights. ACCRF intends to support the curation, analysis and dissemination of this knowledge to all interested researchers.

    Preclinical Drug Screening

    Preclinical drug screens are an important element in the deciding whether to move forward with a clinical trial of a particular drug in a specific tumor type. Basic research may implicate and validate molecular targets, but the first proof of concept that a drug will work in a patient population lies in preclinical models.

    Many drug discovery efforts include a high-throughput screen of thousands or millions of compounds in disease-specific cell lines. The lack of any valid ACC cell lines necessitates a different and more rational approach. ACCRF has patient-derived xenograft models of ACC that are lower-throughput and more expensive than cell lines. Accordingly, the xenograft screens are limited to (1) baseline screens of standard anticancer agents to assess overall model sensitivities, (2) drugs that are in clinical trials for ACC patients to assess whether the models are predictive of clinical efficacy, and (3) novel drugs that inhibit targets implicated in ACC by basic research projects. These xenograft studies are carried out on behalf of ACCRF by South Texas Accelerated Research Therapeutics (START) on a contractual basis.

    The gene MYB is clearly implicated in ACC and certain leukemias. ACCRF supports a project at Harvard University that identifies compounds that suppress MYB expression in genetically modified zebrafish.

    Clinical Trials

    The goal of the Research Agenda is to get effective drugs to patients. Given the rarity of ACC, it is neither feasible nor desirable to cycle through as many clinical trials as possible to achieve our goal. Instead, the focus must be on generating a few high quality studies with clear scientific rationales related to known mechanisms of action, supportive preclinical screening data and, if possible, anecdotes of clinical activity. Patients are more likely to enroll in such clinical trials and private biopharmaceutical firms and the NIH are more likely to sponsor such clinical trials.

    ACCRF collaborates with its affiliated researchers to not only access novel drugs for preclinical screening, but also to approach biopharmaceutical companies about sponsoring high quality clinical trials in ACC. The strategy has already been successful for an FGFR inhibitor and a pipeline of worthwhile concepts is in process. The foundation has demonstrated its ability to orchestrate the development of a complete translational concept and to educate the patient community about promising studies.