Interview with Prof. Gad Rennert, Director, Clalit National Israeli Cancer Control Center

Dr. Rennert directs a national center in Israel which is responsible for research and implementation of the personalized medicine approach in the health system. With an MD (1984, Ben Gurion U, Israel) and PhD in Public Health (1988, UNC, Chapel Hill) he is a trained molecular epidemiologist and experienced public health genomics professional and has published extensively in these fields. His Center is responsible for approval of all molecular testing in Clalit Health Services – the largest health care provider in Israel and has more than 40,000 people under current research and a bio-bank with more than 400,000 aliquots of DNA, sera, lymphocytes and tumor tissue. Read his full bio.

Interview with Prof. Gad Rennert, Director, Clalit National Israeli Cancer Control Center

Q: You participated in the OncoArray Consortium that studied genetic variants that contribute to the risk of developing breast cancer. What were the key findings? What impact would it have on breast cancer therapies?

A: The OncoArray consortium was actually studying a pre-designed array of 500K SNPs across 5 tumor sites (breast, colon, lung, ovary, prostate). In contrast with a usual GWAS study, here SNPs of prior interest have enriched a backbone of SNPs spread across the genome. Each one of the five tumor-site specific groups came up with dozens (up to 170 SNPs in the breast cancer group) of SNPs associated with risk increase or risk reduction. All groups are now investing efforts in establishing polygenic risk scores based on an optimal set of the identified SNPs (for example a British group added a set of 88 SNPs as an organ in their breast cancer risk score equation).

Q: How have you used epidemiology studies to better screen for cancer among different Israeli demographic (Jews/Arabs, men/women, immigrants/natives, elderly/young) groups?

A: Demographic differences have always served us as means of understanding disease etiology and designing prevention intervention. The addition of genetic knowledge to simple demographic/ethnic parameters allows us to better tailor our policies. We have shown smoking to be of different risk effect in Jews and Arabs and founder mutations in Ashkenazi Jews to easily identify groups at high risk of breast or colon cancer. High risk groups, once identified, can be offered more intensive screening (in terms of age at beginning, intensity, type of screening modality) and the current expert opinion in the field of breast cancer screening with mammography, for example, suggests that in the near future we will desert the age related algorithm and move to a risk related algorithm (including elements such as breast density, polygene score etc.) to dictate who should test and at what intensity.

Q: What are some of the challenges to realize precision healthcare in Israel?

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A: The standardized, centralized, health provision system in Israel should theoretically make implementation of precision medicine easier in countries such as Israel. However, two major barriers are ahead of us; one is the lack of hard evidence of a clear clinical or economic macro benefit of the precision approach (while we believe that such exists); another one is the relative lack of enthusiasm of the leaders of the health system (at government of providers level) to make the necessary investments necessary to actually this paradigm shift to occur coupled with a true major lack of resources in the medical system. This is why Clalit Health Services (the largest health services provider in Israel) is planning on entering a randomized trial which will implement various aspects of precision medicine and will measure process (degree of preparedness of population and medical teams, IT means of practicing precision medicine) as well as outcome (clinical and financial) variables to allow decision on a nation-wide scale.

Q: In advanced NSCLC, immunotherapy is evolving to become first-line treatment. What do you see the future of breast cancer care in five years?

A: Immunotheraphy has actually just recently also been shown to be of potentially major importance in the treatment of some of the sub-types of breast cancer. The diagnosis of breast cancer has changed over recent years with the identification of several tumor su-types, first based on hormone receptors status and recently with even deeper biological identifiers. Once a sub-group is identified, it is further biologically and clinically characterized and tumor-type specific prevention, detection and treatment modalities can then be tailored.