5 Questions... with Rafael Fonseca, MD

Published: Thursday, Aug 21, 2008
Rafael Fonseca, MD, is a professor of medicine at Mayo Clinic and a consultant in the Division of Hematology/Oncology. He also serves as deputy director for the Mayo Clinic Cancer Center. In addition, Dr. Fonseca has an adjunct appointment at the Translational Genomics Research Institute, where he works in collaboration with Drs. John Carpten and Jeffrey Trent. Dr. Fonseca concentrates on the genomic nature of late B-cell neoplasms, particularly focused on multiple myeloma. He is interested in the clinical implications for prognosis and treatment selection of specifi c molecular markers in the myeloma cells. Dr. Fonseca worked for 10 years at the Mayo Clinic in Rochester and transferred his research program to the Mayo Clinic in Scottsdale in January 2004.

1 What is your primary focus at the Translational Genomics Research Institute?

I have a joint appointment at TGen with a goal of participating in joint projects relating to the genetics and genomics of multiple myeloma. In partnership with Dr. John Carpten, we have been successful in establishing a large number of genomic studies that have already resulted in joint grant applications as well as high-profile publications. Mayo brings research expertise at the laboratory level, as well as the clinical expertise for understanding the implications of new findings. Working with scientists such as Dr. Carpten, we were able to leverage some of the great power of TGen genomic tools, such as the array-based comparative genomic hybridization (aCGH). Together, we have tried to tackle one of the challenges in genomics research—how to integrate all of the information related to the sample quality, clinical features associated with the samples, data associated from the DNA copy number, gene expression profiling, etc. In one example, our team found that NF-kappa B was constitutively activated in up to 50% of myeloma patients.

2 What have been some of your successes over the last four years since joining the team?

Since I came to Mayo in 2004, I was fortunate to have worked with two great friends and colleagues, Drs. Leif Bergsagel and Keith Stewart. We had long talked about the possibility of joining forces and working together toward applying genetics and early drug development for the treatment of myeloma. We were successful in recruiting Dr. Bergsagel nine months after my arrival in Arizona and Dr. Stewart the year following that. I consider the formation of this team one of my biggest successes. We now have a laboratory meeting that encompasses up to 20 individuals, including postdoctoral fellows, research technologists, and principal investigators. These individuals come from all over the world, including Singapore, New Zealand, Argentina, Brazil, Canada, and Mexico. This is a highly collegial team, but nevertheless competitive, and in a short period, we have been able to produce a large stream of publications. However, our greatest success is our ability to translate some of these findings and research to the clinic. Since coming to Arizona, we have had a very significant growth in the number of myeloma patients that we can care for in the clinic and with whom we can work in clinical trials and on basic research projects. We are clearly honored to have this partnership with those individuals who entrust us with their healthcare.

3 What clinical trials are you and your colleagues currently involved with?

We have an ample portfolio of phase I and phase II clinical trials. We have been involved in the development of a third generation of immunomodulatory drug, related to thalidomide and lenalidomide, CC 4047. Currently at Mayo, we are running a clinical trial with CC 4047, which we are hoping to ultimately bring to the clinic. We have also been engaged, primarily through the leadership of Dr. Stewart, in the development of novel proteasome inhibitors, such as carfilzomib. We have participated in the early development of this drug and are currently involved in phase II and phase III clinical trial design. Our team, in conjunction with the Multiple Myeloma Research Consortium, was also the first to lead a clinical trial targeting a specific genetic marker in myeloma. We had a small molecule inhibitor of the oncogene FGFR3 in myeloma patients.

This clinical trial was the first ever attempt to target such genetic lesions in multiple myeloma. Our hearts were really close to the development of that trial because of our close participation in the concept development. Dr. Bergsagel, and his wife Dr. Marta

Chesi, discovered the translocation almost 10 years ago. My laboratory uncovered the clinical implications for this genetic abnormality, and ultimately, the preclinical development of the compound was lead by Dr. Stewart.

4 How has patients’ expanded access to medical information affected clinical care and research?

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