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The PATh to improve treatment for blood cancers

Researchers at Cornell University in Ithaca and Weill Cornell Medical College, led by Drs. Leandro Cerchietti and Kristy Richards, are teaming up to fight hematologic malignancies with a multi-pronged attack that leverages the strengths of both campuses.  Cancer research, particularly research on hematologic malignancies (e.g. lymphoma, leukemia, and multiple myeloma), has been hindered by a lack of accurate model systems.  Using a highly multidisciplinary approach, Cornell researchers aim to change that. Improvements in multiple points along the drug development pipeline, along with a comprehensive, high-throughput, and iterative strategy aims to make the process of drug development (i.e. finding which drugs and combinations of drugs work best on which tumors) more accurate, faster, and more efficient overall.

Lymphoma Program Members


Traditionally, new drugs have first been tested in vitro, using established immortalized cell lines, followed by testing in mouse xenograft models. Mouse xenografts are transplanted human tumors that are grown by implanting them in the subcutaneous tissue of an immunocompromised mouse. Unfortunately, neither of these experimental systems is highly accurate or reliable, such that only about 10% of drugs that make it past these preclinical testing hurdles go on to achieve FDA approval1, driving up the cost of drug development, and slowing the progress of new drugs to the clinic.


Cornell's Progressive Assessment of Therapeutics (PATh) program combines a multi-tiered program to improve the efficiency of the experimental therapeutics pipeline.  In collaboration with Ankur Singh in the College of Engineering, better three-dimensional tissue culture systems are being developed to enable the in vitro growth of a wider variety of leukemia and lymphoma cells. These "organoids", as they are called, better mimic the cellular environment in which cancer cells grow, and can lead to more representative drug testing screens. Furthermore, organoids can be arrayed so that hundreds of tests can be done simultaneously, allowing high-throughput and automated drug testing.

Lymphoma Pyramid  
Figure 5

The next tier of assessment relies on improved mouse models of two types. The first are genetically engineered mouse models (GEMMs) that are modified to carry specific cancer-causing mutations. The second type of mouse models is immunocompromised mouse strains that allow the growth of implanted human tumors, also known as xenografts, in the host mouse. These mouse "avatars" can then be used as individualized surrogates for drug testing, allowing true personalized medicine approaches. Cornell has strong expertise with both types of these mouse models. John Schimenti leads the transgenic mouse core facility where new technologies such as CRISPR/Cas9 directed mutagenesis are allowing the more rapid development of GEMMs that perfectly mimic human genetic lesions. Giorgio Inghirami is a world expert in lymphoma xenografts, and in concert with Robert Weiss at the College of Veterinary Medicine, leads the patient-derived xenografting program.

The final tier of the PATh pyramid is clinical trials, and here Cornell has an additional advantage.  In addition to world-renowned expertise in early human clinical trials at WCMC, the veterinary clinics in Ithaca (and CUVS) allow for co-clinical trials to be performed in pet dogs (and potentially other species seen in the veterinary clinic as well). This increases the number of patients available for participation in clinical trials and increases the robustness of findings if a drug is effective in treating lymphoma or leukemia in more than one species. It also provides the advantages of early access to new drugs in development for both human and canine patients at Cornell.

Capitalizing on the multi-faceted team of researchers at Cornell, the PATh program provides a synergistic approach that provides a dynamic and powerful strategy for developing new drugs to fight hematologic malignancies and rapidly improving patient care.


1Hay et. al. Clinical Development success rates for investigational drugs. Nature Biotechnology, 32: 40-51, January 9, 2014.

 

 

   
     
 
     
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aboutUSThe Comparative Cancer Biology Program at Cornell University is a new initiative supported by the College of Veterinary Medicine to establish comprehensive interdisciplinary training and facilitate rigorous hypothesis-driven research in comparative cancer biology. The program brings together clinical and basic scientists at the College of Veterinary Medicine and promotes synergistic interactions with other investigators throughout Cornell University. Currently, the program supports the research activities of several graduate students, postdoctoral fellows, and veterinary residents through competitive training awards. The program also sponsors a University-wide cancer symposium, College-wide mini-seminar series in cancer biology and an annual retreat.
 
 
 
     
 
 

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