PMID- 30912023
OWN - NLM
STAT- MEDLINE
DCOM- 20190717
LR  - 20190717
IS  - 1940-6029 (Electronic)
IS  - 1064-3745 (Linking)
VI  - 1953
DP  - 2019
TI  - In Vivo Pharmacology Models for Cancer Target Research.
PG  - 183-211
LID - 10.1007/978-1-4939-9145-7_12 [doi]
AB  - Experimental animal tumor models have been broadly used to evaluate anticancer 
      drugs in the preclinical setting. They have also been widely applied for drug 
      target discovery and validation, which usually follows four experimental 
      strategies: first, assess the roles of putative drug targets using in vivo 
      tumorigenicity and tumor growth kinetics assays of transplanted tumors, 
      engineered through gain-of-function (GOF) by overexpressing transgene or knock-in 
      (KI) or loss-of-function by gene silencing using knockdown (KD) or knockout (KO) 
      or mutation via mutagenesis procedures; second, similarly genetically engineered 
      mouse models (GEMM), through either germline or somatic cell procedures, are used 
      to test the roles of potential targets in spontaneous tumorigenicity assays; 
      third, patient-derived xenografts (PDXs), which most closely resemble patient 
      genetics and histopathology, are used in tumor inhibition assays for evaluating 
      target-/pathway-specific inhibitors, including large and small molecules, thus 
      assessing the drug target; and fourth, the targets can be assessed in 
      population-based trials, mouse clinical trials (MCT), so that the validation can 
      be generally meaningful as performed in human clinical trials. This chapter 
      outlines the commonly used protocols in cancer drug target research: the first 
      four sections describe four sets of different, specific pharmacology protocols 
      used in the respective cancer modeling stages, with the last section summarizing 
      the common protocols applicable to all four pharmacology modeling steps.
FAU - Chen, Dawei
AU  - Chen D
AD  - Crown Bioscience Inc., San Diego, CA, USA.
FAU - An, Xiaoyu
AU  - An X
AD  - Crown Bioscience Inc., San Diego, CA, USA.
AD  - State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 
      China.
FAU - Ouyang, Xuesong
AU  - Ouyang X
AD  - Crown Bioscience Inc., San Diego, CA, USA.
FAU - Cai, Jie
AU  - Cai J
AD  - Crown Bioscience Inc., San Diego, CA, USA.
FAU - Zhou, Demin
AU  - Zhou D
AD  - State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 
      China.
FAU - Li, Qi-Xiang
AU  - Li QX
AD  - Crown Bioscience Inc., San Diego, CA, USA. henryli@crownbio.com.
AD  - State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, 
      China. henryli@crownbio.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Methods Mol Biol
JT  - Methods in molecular biology (Clifton, N.J.)
JID - 9214969
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Carcinogenesis/drug effects/genetics/pathology
MH  - Cell Line, Tumor
MH  - Drug Discovery/*methods
MH  - Gene Targeting/*methods
MH  - Humans
MH  - Mice
MH  - Molecular Targeted Therapy/methods
MH  - Neoplasms/*drug therapy/genetics/pathology
MH  - Neoplasms, Experimental/drug therapy/genetics/pathology
MH  - Transgenes
MH  - Tumor Burden/drug effects
MH  - Xenograft Model Antitumor Assays/*methods
OTO - NOTNLM
OT  - GEMM
OT  - Homograft
OT  - Knock-in
OT  - Knockdown
OT  - Knockout
OT  - PDX
OT  - Transgene
OT  - Tumor growth inhibition
OT  - Tumor growth kinetics
OT  - Tumorigenesis
OT  - Xenograft
EDAT- 2019/03/27 06:00
MHDA- 2019/07/18 06:00
CRDT- 2019/03/27 06:00
PHST- 2019/03/27 06:00 [entrez]
PHST- 2019/03/27 06:00 [pubmed]
PHST- 2019/07/18 06:00 [medline]
AID - 10.1007/978-1-4939-9145-7_12 [doi]
PST - ppublish
SO  - Methods Mol Biol. 2019;1953:183-211. doi: 10.1007/978-1-4939-9145-7_12.