For Researchers: The Precision Medicine Molecular Tumor Board


Most cancers have alterations in genes resulting in either over-activation of cellular signaling pathways or loss of tumor suppressor function. Many of these molecular changes are believed to be “passenger” genomic alterations, which are presumed to produce changes that have only a small effect on cancer growth and progression.  Therefore, identifying the genomic alterations that “drive” the cancer is critically important in selecting effective genomically targeted therapies. The ability to distinguish genomic “drivers” from “passengers” and to recognize particular genomic alterations as potentially “actionable” requires a high level of expertise across multiple medical and scientific areas. These disciplines, including population genetics, cancer biology, and clinically applied bioinformatics, have not typically been part of the training of most oncologists or many of the members of the more traditional multidisciplinary cancer care teams.

DNAIn order to address these needs and support decision making and access to targeted treatment for patients with rare tumors or advanced tumors that are resistant to standard therapy, a clinical trial incorporating a multispecialty molecular tumor board meets weekly at the Rutgers Cancer Institute of New Jersey. The areas of specialty of members of the molecular tumor board are diverse and include medical and surgical oncology, basic science, bioinformatics, genetic counseling, systems biology, pathology, tumor and population genetics, and clinical trial specialists.

The presentation of cases in both traditional and molecular tumor boards is likely to begin with a summary of patient characteristics, treatment history, as well as a pathologic review of the tumor. However, unlike traditional tumor boards, molecular tumor boards are focused on an analysis of the mutational landscape of the genome of the tumor, not its site of origin; in fact, the cases presented at a typical meeting of the molecular tumor board at the Rutgers Cancer Institute of New Jersey are likely to include a discussion of tumors with several different tissue types or from various sites of origin both in children and adults.

precision medicinePatient cases for review by the molecular tumor board come from within the institute as well as from community oncology practices. The Precision Medicine team physicians start the review process by evaluating the history of each patient, and the genomic profile of the patients’ tumors. After hours of research on the part of a Precision Medicine team physician, the molecular tumor board convenes and each case is formally presented. Following lively and highly informed discussions between the diverse members of the molecular tumor board, the Board reaches a consensus regarding the interpretation of genomic data from tumor specimens and their clinical implications for the individual patient within the context of the most recent published research. Recommendations from the molecular tumor board are then summarized in a formal letter sent to the treating physician. Researchers subsequently follow up with the treating physician for updates on each patient’s condition.

From the discussions at the molecular tumor board, new research questions emerge and are discussed.  For example, a translational laboratory within the precision medicine program performed an assay reinforcing the hypothesis that melanoma harboring both a BRAFV600E mutation and a BRAF translocation responds to the combination of a BRAF inhibitor and a MEK inhibitor, but not a BRAF inhibitor alone, as seen in a patient case1.  Consequently, the presentation of clinical cases at the molecular tumor board can initiate critical laboratory research, which could contribute to a better understanding of precision medicine and help guide clinical decision-making.

Articles on topics stemming from the molecular tumor board or individual case studies have been published.  For example, an article observing a patient with endometrial cancer and a mutation in the gene POLE determined that treatment with the anti-PD-1 inhibitor, pembrolizumab, had prolonged response to the therapy2.  Computational biologists elucidated data from TCGA on various subsets of endometrial cancer, determining that POLE-mutated cancers had higher expression of genes involved in immunologic activity2.  Also, an article published in Gynecologic Oncology focused on the analyses of tumor genes in gynecologic cancers through comprehensive genomic profiling, along with the feasibility and clinical utility of recommendations formed based on this genomic profiling in the context of a molecular tumor board in the precision medicine clinical trial3.  This article found that as more patients were added to this clinical trial, the greater the level of acceptance and adherence became among the treating physicians to the recommendations provided by the precision medicine team3.  As more patients enter this clinical trial, the experience and knowledge of the molecular tumor board and the practice of precision medicine are increasingly enhanced.

The molecular tumor board meets at the Rutgers Cancer Institute of New Jersey every Friday morning between 9:30 am and 11:00 am. Physicians, nurses, scientists, physician scientists, biostatisticians, pathologists, and clinical trial specialists are welcome to attend as long as they have previously completed the appropriate Collaborative Institutional Training Initiative (CITI) training. To receive information about the meeting and be included on the mailing list, please contact Natasha Nicholson, Staff Assistant, at 732-235-7559.  
 

  1. Kulkarni A HK, Chen S, Pine SR, Jeyamohan C, Sokol L, Ali SM, White E, Rodriguez-Rodriguez L, Mehnert JM, Ganesan S. BRAF fusion as a novel mechanism of acquired resistance to vemurafenib in BRAF V600E mutant melanoma. (submitted work). 
     
  2. Mehnert JM PA, Zhong H, Hirshfield K, Damare S, Lane K, Sokol L, Stein MN, Rodriguez-Rodriguez L, Kaufman HL, Ali S, Ross JS, Pavlick DC, Bhanot G, White EP, DiPaola RS, Lovell A, Cheng J, Ganesan S. Immune activation and response to pembrolizumab in a POLE-mutant endometrial cancer. J Clin Invest. 2016 (in press)PubMed PMID: 27159395.
     
  3. Rodriguez-Rodriguez L, Hirshfield KM, Rojas V, et al. Use of comprehensive genomic profiling to direct point-of-care management of patients with gynecologic cancers. Gynecol Oncol. 2016;141(1):2-9. PubMed PMID: 27016222.  

 

 

 

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