PAAR4Kids Profile
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PAAR4Kids

Pharmacogenomics of Anticancer Agents Research in Children

Website

http://www.pharmacogenetics.org/paar4kids/

Principal Investigator

Mary V. Relling, Pharm.D.

Host Institution

St. Jude Children's Research Hospital, Memphis, TN

Grant Number

GM92666

PGRN 2010 Retreat Poster

PAAR4Kids Poster

Publications

PAAR4Kids Publications

Top Publications

PAAR4Kids Publications

Abstract (Updated as of March 2015)

The goal of PAAR4Kids is to fully define the pharmacogenomics of childhood acute lymphoblastic leukemia (ALL), the most common childhood malignancy, in order to improve the lives of children with this disease, as well as any patients treated with the same medications.

Our aims are to define genomic variations (germline and acquired) important for interpatient variability in treatment response and toxicity from medications used to treat childhood ALL, to translate pharmacogenomics into clinical treatment strategies, and to collaborate with pharmacogenomics investigators to leverage relevant pharmacogenomic knowledge from pediatric ALL to other diseases and disciplines (and vice-versa). This is accomplished by a multidisciplinary team of leaders in the field.

The research harnesses the power of studying patients with ALL treated on Children's Oncology Group (COG) and St. Jude Children's Research Hospital protocols, achieving near-population-level coverage for ALL in the US. Pediatric ALL provides outstanding opportunities for pharmacogenomic discoveries and translation to the clinic, because this is an otherwise fatal disease that is cured through extensive use of agents that have a narrow therapeutic index. The agents are broadly used in cancer and in general medical practice and thus the findings from PAAR4Kids have applicability outside of pediatric ALL, as demonstrated by multiple collaborations within and outside of the PGRN. PAAR4Kids studies the pharmacogenomics, pharmacokinetics (cellular and plasma), antileukemic and toxic effects of glucocorticoids, methotrexate, thiopurines, asparaginase, anthracyclines, and vincristine.

The approach is summarized in four major Steps. In Step 1 genotype/phenotype studies are undertaken in a set of core phase III front-line clinical trials involving over 10,000 patients that serve as discovery and replication cohorts. Non-genetic covariates are included. In Step 2, genomic variation is prioritized for further follow-up. Step 3 is confirmation and validation, consisting of mechanistic experimental laboratory models, surveys of human tissues, and/or additional genotype/phenotype analyses in other clinical trials, often using PGRN resources. In Step 4, validated genomic associations with large effect sizes are integrated into clinical settings.

To expand on Step 4, PAAR4Kids has taken a leading role in the Clinical Pharmacogenetics Implementation Consortium (CPIC), a collaboration between the PGRN and PharmGKB. CPIC is creating and making publicly available specific clinical guidelines for modifying therapy based on genetic test results (https://www.pharmgkb.org/page/cpic ). PAAR4Kids is an active member of the PGRN’s TPP, and as part of its PG4KDS protocol (www.stjude.org/pg4kds ), PAAR4Kids is implementing CPIC clinical guidelines into all of patient care at St. Jude (patients with and without cancer), using computational decision support tools to guide prescribing.

PAAR4Kids has world class scientists applying state-of-the-art genomics techniques to the germline and tumor cells of impeccably cataloged specimen collections from extensively phenotyped patients, and outstanding statisticians, pharmacologists, and clinicians. PAAR4Kids is poised to comprehensively attack the pharmacogenomics of childhood ALL, and to implement pharmacogenomics into patient care.

Team Members

St. Jude Team

Mary V. Relling, Pharm.D.
Principal Investigator
Email: mary.relling@stjude.org
Phone: (901) 595-2348

William E. Evans, Pharm.D.
Co-Investigator
Email: william.evans@stjude.org
Phone: (901) 595-3301

Jun J. Yang, Ph.D.
Co-Investigator
Email: jun.yang@stjude.org
Phone: (901) 595-2517

Cheng Cheng, Ph.D.
Investigator
Email: cheng.cheng@stjude.org
Phone: (901) 595-2935

Wenjian Yang, Ph.D.
Co-Investigator
Email: wenjian.yang@stjude.org
Phone: (901) 595-4800

Erin G. Schuetz, Ph.D.
Co-Investigator
Email: erin.schuetz@stjude.org
Phone: (901) 595-2149

Ching-Hon Pui, M.D.
Co-Investigator
Email: ching-hon.pui@stjude.org
Phone: (901) 595-4329

James Downing, M.D.
Investigator
Email: james.downing@stjude.org
Phone: (901) 595-3956

Charles Mullighan, M.D.
Investigator
Email: Charles.mullighan@stjude.org
Phone: (901) 595-3387

Geoffrey Neale, Ph.D.
Co-Investigator
Email: Geoffrey.neale@stjude.org
Phone: (901) 595-3284

Deqing Pei, Ph.D.
Investigator
Email: deqing.pei@stjude.org
Phone: (901) 595-3076

Laura Ramsey, Ph.D.
Investigator
Email: laura.ramsey@stjude.org
Phone: (901) 595-8716

John Schuetz, Ph.D.
Co-Investigator
Email: john.schuetz@stjude.org
Phone: (901) 595-2174

Dawn Bowen
Project Manager
Email: Dawn.bowen@stjude.org
Phone: (901) 595-3663

  

University of California, San Francisco

Mignon Loh, M.D.
Co-Investigator
Email: lohm@peds.ucsf.edu
Phone: (415) 476-3831

   

University of Florida, Gainesville

Meenakshi Devidas, Ph.D.
Investigator/ Statistician
Email: mdevidas@cog.ufl.edu
Phone: (352) 273-0551

   

Nationwide Children's Hospital, Columbus, OH

Julie Gastier-Foster, Ph.D.
Co-Investigator
Email: julie.gastier-foster@nationwidchildrens.org
Phone: (614) 722-270

 

  

City of Hope, Duarte, CA

Smita Bhatia, M.D.
Co-Investigator
Email: sbhatia@uab.edu 
 Phone: 205-638-2122

   

University of Texas MD Anderson Cancer Institute, Houston

Paul Scheet, Ph.D.
Investigator
Email: permutations@gmail.com
Phone: (713) 745-2470

   

John Hopkins University, Baltimore, MD

Gary Rosner, Ph.D.
Investigator
Email: grosner1@jhmi.edu
Phone: (410) 955-4884

   
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