Research & Publications †
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Biographical Sketch
Ram Ganapathi, Ph.D., is Director of the Clinical Pharmacology Program at the Taussig Cancer Institute, Cleveland Clinic.
The laboratory of clinical pharmacology within the Experimental Therapeutics Program of the Cleveland Clinic Taussig Cancer Institute was originally established in spring of 1982 with a laboratory program focused on mechanisms by which cancer cells evade chemotherapy. This program has been continuously supported by the National Cancer Institute and National Institutes of Health for more than 25 years, and it is built on the strong belief that rational and effective treatment of cancer requires a comprehensive understanding of the biology of the tumor being treated as well as an understanding of the mechanisms of action and pathways that regulate resistance to the anti-cancer drug.
This information is integrated in drug development and Phase I clinical trials that are focused on defining safety and toxicity of new drugs being tested in patients with cancer. Keeping these goals in perspective, promising experimental results from the laboratory and an understanding of regulation of genes in the cancer are actively pursued in translational studies for targeted therapy in kidney cancer, leukemia and ovarian cancer, to maximize efficacy and reduce toxicity of cancer chemotherapy.
Our studies in acute myeloid leukemia (AML), a form of leukemia commonly found in adults are focused on an enzyme called topoisomerase II that is essential for cell division and involved in cell differentiation in mammalian cells. Towards understanding the regulation of topoisomerases during cell growth and differentiation, our studies are focused on determining the regulatory function of topoisomerase IIa and ß as down stream effectors of all trans retinoic acid-induced effects on cell growth and differentiation in models of human AML and leukemia cells from patients with AML.
This enzyme is also a target for several anti-cancer drugs that are widely used to treat patients with leukemia, breast cancer and lung cancer, and our studies with topoisomerase II have revealed that the defective addition of phosphate at specific sites in the enzyme is a mechanism by which tumor cells evade chemotherapy. Using results from laboratory engineered model systems to understand how the addition of phosphate makes this enzyme vulnerable to drug treatment, leukemia cells from patients with AML are being tested to develop novel treatment strategies.
Our work in kidney cancer and ovarian cancer are focused on understanding how the screening for specific genes or mutations in a gene can be used to predict the effects of targeted therapy and treatment failure. Based on the recent identification of a few important genes in these cancers, we are studying their regulation to develop new paradigms for targeted therapy and novel treatment options when relapse from the cancer is a problem.
Specialty Interests
Clinical Pharmacology, clinical pharmacology and experimental cancer chemotherapy
Industry Relationships
Cleveland Clinic physicians and scientists may collaborate with the
pharmaceutical or medical device industries to help develop medical
breakthroughs or provide medical expertise or education. Cleveland Clinic
strives to make scientific advances that will benefit patient care and
support outside relationships that promise public benefit. In order for
the discoveries of Cleveland Clinic physicians' and scientists'
laboratories and investigations to benefit the public, these discoveries
must be commercialized in partnership with industry. As experts in their
fields, Cleveland Clinic physicians and scientists are often sought after
by industry to consult, provide expertise and education.
To assure professional and commercial integrity in such matters,
Cleveland Clinic maintains a program that reviews these collaborations
and, when appropriate, puts measures in place to minimize bias that may
result from ties to industry. The Cleveland Clinic publicly discloses
the names of companies when (i) its physicians/scientists receive $5,000
or more per year (or, in rare cases, equity or stock options) for speaking and consulting, (ii) its
physicians/scientists serve as a fiduciary, (iii) its physicians/scientists
receive or have the right to receive royalties or (iv) its
physicians/scientists hold any equity interest for the
physician's/scientist's role as inventor, discoverer, developer, founder
or consultant.* In publicly disclosing this information, the Cleveland
Clinic tries to provide information as accurately as possible about its
physicians' and scientists' connections with industry.
As of 3/12/2010, Dr. Ganapathi has reported no financial relationship
with industry that is applicable to this listing. In general, patients
should feel free to contact their doctor about any of the relationships
and how the relationships are overseen by the Cleveland Clinic. To learn
more about the Cleveland Clinic's policies on collaborations with industry
and innovation management, go to our
Integrity in Innovation
page.
* Cleveland Clinic physicians and scientists subscribe to the guidance presented in the PhRMA Code on Interactions with Healthcare Professionals and the AdvaMed Code of Ethics on Interactions with Health Care Professionals. As such, gifts of substantial value are generally prohibited.
