Xenograft models for pediatric cancer therapies

Abstract

The prognosis for childhood cancer has improved considerably over the past 50 years. This improvement is attributed to well-designed clinical trials which have incorporated chemotherapy, surgery, and radiation. With an increased understanding of cancer biology and genetics, we have entered an era of precision medicine and immunotherapy that provides potential for improved cure rates. However, preclinical evaluation of these therapies is more nuanced, requiring more robust animal models. Evaluation of targeted treatments requires molecularly defined xenograft models that can capture the diversity within pediatric cancer. The development of novel immunotherapies ideally involves the use of animal models that can accurately recapitulate the human immune response. In this review, we provide an overview of xenograft models for childhood cancers, review successful examples of novel therapies translated from xenograft models to the clinic, and describe the modern tools of xenograft biobanks and humanized xenograft models for the study of immunotherapies.

Addressing a Pre-Clinical Pipeline Gap: Development of the Pediatric Acute Myeloid Leukemia Patient-Derived Xenograft Program at Texas Children’s Hospital at Baylor College of Medicine

“…Patient-derived xenograft (PDX) models are the gold standard for pre-clinical novel agent evaluation [9,10]. These models are created by transplanting human cancer cells into immunodeficient mice (IDM), allowing for the faithful replication of the human tumor in a live animal model [9,11].…”

“…Patient-derived xenograft (PDX) models are the gold standard for pre-clinical novel agent evaluation [9,10]. These models are created by transplanting human cancer cells into immunodeficient mice (IDM), allowing for the faithful replication of the human tumor in a live animal model [9,11]. PDX models have been successful in pre-clinical drug testing, accurately reflecting the genetic and biological heterogeneity of the human disease and its response to treatment [12].…”

“…Many cancer subtypes have large collections of PDX models available for pre-clinical testing [13]. These collections allow novel agents to be tested in multiple different genetic subtypes to understand ranges of responses [9]. Historically, however, developing PDX models from AML patients has been difficult.…”

“…In contrast, few pAML PDX models exist for several reasons, including limited patient numbers, the lack of specialized techniques and expertise required to generate models, and a shortage of financial incentive to develop models for a relatively rare disease [9]. A handful of researchers have successfully developed some pAML PDX models [16][17][18][19][20][21].…”