February, 2017
The University of Michigan Adrenal Cancer Program
Adrenal cancer or adrenal cortical carcinoma (ACC) is one of the rarest and most deadly cancers. The only approved treatment for ACC is a derivative of a pesticide, which may not be well-tolerated by all patients.
Because it is not a commonly occurring cancer, research funding for ACC is scarce. Tremendous collaboration between institutions is necessary to amass enough patient data to generate meaningful research findings.
Through clinical care, research, advocacy and education, clinicians and scientists in the U-M adrenal cancer program are working to overcome such obstacles.
U-M currently treats more adrenal cancer patients and trains more specialists than any other institution in the world.
CLINICAL CARE
Part of the U-M Endocrine Oncology Program, our Adrenal Cancer Clinic is one of only a handful of multidisciplinary referral centers for ACC in the world. Specialists in endocrinology and endocrine surgery, medical oncology, genetics, radiation oncology, nuclear medicine and more come together to provide diagnoses and rare disease management for patients from across the globe.
In addition to caring for patients in the clinic, the U-M adrenal team piloted a Remote Second Opinion Program to improve access to multidisciplinary care for patients who are not able to travel to U-M. Records, films and pathology reports are presented at the U-M Adrenal Cancer Tumor Board, where an opinion on patient care and progress is rendered. Whereas in-person consultations are always preferable, this service provides the next best thing for patients and families with no other treatment alternatives.
RESEARCH
U-M’s basic research in adrenal cancer focuses on the genetics of adrenal cancer. Areas of study include 1) the biology of adrenal cortical stem cells and the pathways that regulate them, 2) tumor differentiation (homeostasis) and how defects in the genes that regulate differentiation develop and function, and 3) the genetics of inherited/familial adrenal tumors.
U-M investigators played a pivotal role in convincing the National Cancer Institute-sponsored Cancer Genome Atlas Research Network (TCGA) to include ACC among the cancers to be studied. This is a remarkable achievement in rare disease research. As a result, a recently-published, U-M-led TCGA project identified genes that drive adrenal cancer development. These discoveries open the door to exciting new therapeutic targets.
Clinical and translational research at U-M focuses on international and industry partnerships to develop and test therapeutic agents, and on efforts to leverage serum steroid biomarkers to improve detection and evaluate treatment response. Below are three examples:
- The U-M Adrenal Cancer Program was instrumental in conducting the first industry-sponsored international randomized phase 3 clinical trial of an investigational drug in ACC. The study involved 40 specialty centers in 12 countries. Whereas patients receiving the drug (linsitinib) fared no better than those receiving a placebo, a small subset of patients had a significant response. The team’s next step is to evaluate the DNA collected during the study to identify possible markers for response to this therapy.
- The targeted therapeutic ATR-101, developed at U-M, selectively kills adrenal cancer cells through a novel cholesterol-dependent mechanism that has little impact on other cells in the body. ATR-101 is now available through the U-M biopharmaceutical startup company Millendo Therapeutics. U-M is now one of five institutions offering the phase I study of the safety and tolerability of ATR-101 in patients whose advanced adrenal cancer has progressed while on standard therapy.
- Using mass spectrometry, U-M researchers are characterizing and measuring a number of serum steroid biomarkers to diagnose and monitor treatment of adrenal diseases including ACC, Conn syndrome, congenital adrenal hyperplasia and Cushing syndrome. These biomarkers have the potential to help diagnosticians differentiate between benign and malignant adrenal tumors more reliably, efficiently and safely than current imaging techniques.
INTERNATIONAL COLLABORATION
The U-M Adrenal Cancer Program plays a pivotal role in two international consortia of researchers and clinicians: the European Network for the Study of Adrenal Tumors (ENSAT), founded in 2002, and the American Australian Asian Adrenal Alliance (A5) which U-M helped create to facilitate adrenal research in the rest of the world. These groups are both vital conduits for leveraging financial resources globally to help fund more robust cloud-based data repositories and standard treatment guidelines for adrenal disease.
EDUCATION
In 2003 U-M held the first International Adrenal Cancer Symposium, the only such meeting of its kind. U-M has hosted and/or chaired each symposium held since then. U-M clinician-scientists also played a key role in publishing one of the only textbooks on ACC.
ADVOCACY
The U-M Adrenal Cancer Program director Gary Hammer, M.D., Ph.D. is front and center in the national dialogue on rare cancers. He works with legislators in Washington, D.C., and he and members of his team serve as top advisers on adrenal cancer within the National Cancer Institute and the Endocrine Society.
Led by Dr. Hammer, the U-M team has established itself as a driving force in policy initiatives to increase research funding for rare diseases in general and adrenal cancer specifically.
A deeper dive:
To find out more about the history, creativity and commitment that drive adrenal cancer research and care at U-M, view Dr. Gary Hammer’s TED TALK, “Vulnerability and Presence in Science and Medicine.”