Translating human cancer sequences into personalized porcine cancer models

Chunlong Xu, Sen Wu, Lawrence B Schook, Kyle M. Schachtschneider

Research output: Contribution to journalReview article

Abstract

The global incidence of cancer is rapidly rising, and despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. Cancer is caused by the accumulation of a series of gene mutations called driver mutations that confer selective growth advantages to tumor cells. As cancer therapies move toward personalized medicine, predictive modeling of the role driver mutations play in tumorigenesis and therapeutic susceptibility will become essential. The development of next-generation sequencing technology has made the evaluation of mutated genes possible in clinical practice, allowing for identification of driver mutations underlying cancer development in individual patients. This, combined with recent advances in gene editing technologies such as CRISPR-Cas9 enables development of personalized tumor models for prediction of treatment responses for mutational profiles observed clinically. Pigs represent an ideal animal model for development of personalized tumor models due to their similar size, anatomy, physiology, metabolism, immunity, and genetics compared to humans. Such models would support new initiatives in precision medicine, provide approaches to create disease site tumor models with designated spatial and temporal clinical outcomes, and create standardized tumor models analogous to human tumors to enable therapeutic studies. In this review, we discuss the process of utilizing genomic sequencing approaches, gene editing technologies, and transgenic porcine cancer models to develop clinically relevant, personalized large animal cancer models for use in co-clinical trials, ultimately improving treatment stratification and translation of novel therapeutic approaches to clinical practice.

Original languageEnglish (US)
Article number00105
JournalFrontiers in Oncology
Volume9
Issue numberFEB
DOIs
StatePublished - Jan 1 2019

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Swine
Neoplasms
Precision Medicine
Mutation
Technology
Therapeutics
Clustered Regularly Interspaced Short Palindromic Repeats
Animal Models
Genes
Molecular Biology
Cause of Death
Immunity
Anatomy
Carcinogenesis
Clinical Trials

Keywords

  • Clinical needs
  • Exome sequencing
  • Gene editing
  • Personalized cancer models
  • Translational research

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Translating human cancer sequences into personalized porcine cancer models. / Xu, Chunlong; Wu, Sen; Schook, Lawrence B; Schachtschneider, Kyle M.

In: Frontiers in Oncology, Vol. 9, No. FEB, 00105, 01.01.2019.

Research output: Contribution to journalReview article

Xu, Chunlong ; Wu, Sen ; Schook, Lawrence B ; Schachtschneider, Kyle M. / Translating human cancer sequences into personalized porcine cancer models. In: Frontiers in Oncology. 2019 ; Vol. 9, No. FEB.
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