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Cancer Chemother Pharmacol. 2016 Aug;78(2):221-32. doi: 10.1007/s00280-016-3042-6. Epub 2016 May 18.

Identifying novel therapeutic agents using xenograft models of pediatric cancer.

Author information

1
Greehey Children's Cancer Research Institute, UTHSCSA, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3000, USA.
2
Greehey Children's Cancer Research Institute, UTHSCSA, 8403 Floyd Curl Drive, San Antonio, TX, 78229-3000, USA. HoughtonP@uthscsa.edu.

Abstract

In the USA, the overall cure rate for all childhood cancers is seventy percent, and in many patients that ultimately fail curative therapy, initial responses to current multimodality treatments (surgery, radiation therapy and chemotherapy) is good, with overall 5-year event-free survival approaching 80 %. However, current approaches to curative therapy result in significant morbidity and long-term sequelae, including cardiac dysfunction and cognitive impairment. Furthermore, dose-intensive chemotherapy with conventional agents has not significantly improved outcomes for patients that present with advanced or metastatic disease. Classical cytotoxic agents remain the backbone for curative therapy of both hematologic and solid tumors of childhood. While 'molecularly' targeted agents have shown some clinical activity, responses are often modest and of short duration; hence, there is a need to identify new classes of cytotoxic agent that are effective in patients at relapse and that have reduced or different toxicity profiles to normal tissues. Here we review the pediatric preclinical testing program experience of testing novel agents, and the value and limitations of preclinical xenograft models and genetically engineered mouse models for developing novel agents for treatment of childhood cancer.

KEYWORDS:

Cytotoxic drugs; Human tumor xenografts; Pediatric tumor xenografts

PMID:
27193096
PMCID:
PMC4966996
DOI:
10.1007/s00280-016-3042-6
[Indexed for MEDLINE]
Free PMC Article

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