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Background: Cancer therapeutics and diagnostics have historically tried to leverage gross, observable differences between transformed and normal cells. The realization that chromosomal differences are often correlated with specific cancers provided an entirely new approach which based diagnostics and therapeutics on specific knowledge about the etiology of cancer and likelihood of response to treatmen
Over the past 20 years, researchers at the University of California have developed a comprehensive portfolio of proprietary compositions and methods that marry traditional therapeutic approaches with the targeting of specific pathways compromised by chromosomal deletions known to be associated with specific cancers.
Technology
Diagnostics
Claimed methods allow the detection of chromosomal deletions associated with specific cancers.
Such deletions can sensitize affected cells to specific agents. While applicable to any gene of
interest, methods have been validated for the 9p21 region, which contains the genes coding for
methylthioadenosine phosphorylase (MTAP), p16 and CDK4I. Deletion mapping may indicate cancer
pre-disposition, as well as of the stage of manifest disease.
Therapeutics
MTAP is necessary for:
- conversion of MTA to methionine, required for cellular growth, and
- AMP synthesis through the adenine salvage pathway; AMP is required by cells for both metabolic energy and DNA synthesis.
By targeting pathways dependent on MTAP one can selectively cripple the ability of tumor cells to grow. Indeed, MTAP deficient cancer cells were selectively sensitive to methionine starvation, inhibitors of de novo purine biosynthesis and ATP depletion. These three approaches may be exploited individually or combinatorially for the treatment of MTAP-deficient tumors.
Summary: The ability to target pathways known to be compromised in specific patient populations may provide effective approaches for those most likely to respond to proprietary drugs and methods of treatment. Advantages include:
- Ability to screen patients for chromosomal deletions associated with specific cancers.
- Translatable to any cancer-associated chromosomal deletion
- Proprietary detection methods which allow simple, efficient and low cost screenings
- Increased efficacy and reduced toxicity and non-specific side effects.
While approaches are readily translated to many, known chromosomal deletions, the compositions are directly relevant for cancers associated with 9p21 deletions. This may specifically improve the prognosis for many cancers, including pancreatic, leukemia, NSCLC and mesothelioma.
Keywords: cancer, chemotherapy, diagnostics, targeted therapy, MTAP, pancreatic cancer, NSCLC, leukemia, mesothelioma, p16, INK4A, chromosomal deletions
Related Cases: SD1992-C83, SD1992-D83, SD1994-A91, SD1996-A36, SD1998-B84, SD2002-C35, and SD2006-249.
Research interests can be found at: http://cancer.ucsd.edu/Research/summaries/dcarson.asp
Inquiries To: invent@ucsd.edu
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