September 2007 Mentor of the Month: Martin Fleisher
Martin Fleisher, PhD

Martin Fleisher, PhD, is the Chairman of the Department of Clinical Laboratories and Chief of the Clinical Chemistry Service at the Memorial Sloan-Kettering Cancer Center in New York City. Dr. Fleisher received his doctorate degree in biochemistry from the New York University. Dr. Fleisher has over thirty years experience in discovery and application of new tumor markers and biomarkers for the early detection of cancer.  His interest in biomarkers was initiated by the validation of carcinoembryonic antigen (CEA) in colon cancer.  In 1973 he published the definitive paper on the comparative analytical aspects of three different CEA assays and pointed out the shortcomings of this tumor marker.  His seminal work on the relationship between breast cancer and cystic mastopathy involved over 80 analytes, and included biomarkers consisting of peptides, proteins, enzymes, hormones, immunoglobulins and trace metals.  More than 1500 breast cyst fluids were analyzed and the association of certain analytes to breast cancer was statistically estimated.  He has investigated the use of biomarkers, such as urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1(PAI-1) as prognostic markers in women with node negative breast cancer. 

Dr. Fleisher has spent his career in the discovery, development and clinical association of biomarkers that help in the early detection of cancer.  He developed chromatographic methods for the determination of urinary metabolites used in the early detection and monitoring of neuroblastomas in children.  In collaboration with his neuro-oncology colleagues, he developed a panel of tumor markers in cerebrospinal fluid that help identify the presence of central nervous system tumors (leptomeningeal metastasis).  This panel of biomarkers (AFP, CEA and LDH isoenzyme 5) is still in use today.  In collaboration with his gastrointestinal oncology colleagues, he developed and patented an accurate, highly sensitive test for fecal occult blood that was unaffected by diet, hence reducing false positive test results.  As a member of the International Consortium on Colorectal Cancer and the National Polyp Study Workgroup, he developed and standardized the quality control and clinical use of fecal occult blood testing in the US, Europe, Australia, and Japan.  The successful use of the Hemoccult slide test for detecting early colon cancers is based on the work that Dr. Fleisher and his colleagues published in 1980 and 1983.  The use of high dose methotrexate (MTX) in treating patients with a variety of cancers required the accurate and rapid measurement of MTX in blood and spinal fluid.  Dr. Fleisher developed a semi-automated analytical procedure for the rapid measurement of MTX based on dihydrofolate reductase inhibition, which parallels the pharmacological mode of action of MTX on a cellular level.  The assay is currently used for the measurement of all MTX and anti-fol analogs at MSKCC.  He has developed and validated assays for the management of patients with B-cell dyscrasias with amyloidosis (free serum lambda and kappa light chains), biomarkers helpful in the  prognostic evaluation of patients with ovarian cancer (YKL-40 and MMP-9), the use of circulating tumor cells (CTC) in patients with metastatic prostate cancer, and the development of a bone marker panel (osteocalcin, bone specific alkaline phosphatase, N-telopeptide, and Vitamin D) to detect the affects of tyrosine kinase inhibitors (imatinib) in patients with CML and GIST (NEJM May 2006). 

Dr. Fleisher’s research focus is on the development of new, rapid, and inexpensive bioassays for detecting and monitoring cancer

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