TY - JOUR
T1 - Preclinical Modeling of Pathway-Targeted Therapy of Human Lung Cancer in the Mouse
AU - Vaishnavi, Aria
AU - Kinsey, Conan G.
AU - McMahon, Martin
N1 - Publisher Copyright:
© 2024 Cold Spring Harbor Laboratory Press; all rights reserved;.
PY - 2024/1
Y1 - 2024/1
N2 - Animal models, particularly genetically engineered mouse models (GEMMs), continue to have a transformative impact on our understanding of the initiation and progression of he-matological malignancies and solid tumors. Furthermore, GEMMs have been employed in the design and optimization of potent anticancer therapies. Increasingly, drug responses are assessed in mouse models either prior, or in parallel, to the implementation of precision medical oncology, in which groups of patients with genetically stratified cancers are treated with drugs that target the relevant oncoprotein such that mechanisms of drug sensitivity or resistance may be identified. Subsequently, this has led to the design and preclinical testing of combination therapies designed to forestall the onset of drug resistance. Indeed, mouse models of human lung cancer represent a paradigm for how a wide variety of GEMMs, driven by a variety of oncogenic drivers, have been generated to study initiation, progression, and maintenance of this disease as well as response to drugs. These studies have now ex-panded beyond targeted therapy to include immunotherapy. We highlight key aspects of the relationship between mouse models and the evolution of therapeutic approaches, including oncogene-targeted therapies, immunotherapies, acquired drug resistance, and ways in which successful antitumor strategies improve on efficiently translating preclinical approaches into successful antitumor strategies in patients.
AB - Animal models, particularly genetically engineered mouse models (GEMMs), continue to have a transformative impact on our understanding of the initiation and progression of he-matological malignancies and solid tumors. Furthermore, GEMMs have been employed in the design and optimization of potent anticancer therapies. Increasingly, drug responses are assessed in mouse models either prior, or in parallel, to the implementation of precision medical oncology, in which groups of patients with genetically stratified cancers are treated with drugs that target the relevant oncoprotein such that mechanisms of drug sensitivity or resistance may be identified. Subsequently, this has led to the design and preclinical testing of combination therapies designed to forestall the onset of drug resistance. Indeed, mouse models of human lung cancer represent a paradigm for how a wide variety of GEMMs, driven by a variety of oncogenic drivers, have been generated to study initiation, progression, and maintenance of this disease as well as response to drugs. These studies have now ex-panded beyond targeted therapy to include immunotherapy. We highlight key aspects of the relationship between mouse models and the evolution of therapeutic approaches, including oncogene-targeted therapies, immunotherapies, acquired drug resistance, and ways in which successful antitumor strategies improve on efficiently translating preclinical approaches into successful antitumor strategies in patients.
UR - http://www.scopus.com/inward/record.url?scp=85181760921&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85181760921&partnerID=8YFLogxK
U2 - 10.1101/cshperspect.a041385
DO - 10.1101/cshperspect.a041385
M3 - Article
C2 - 37788883
AN - SCOPUS:85181760921
SN - 2157-1422
VL - 14
JO - Cold Spring Harbor Perspectives in Medicine
JF - Cold Spring Harbor Perspectives in Medicine
IS - 1
M1 - a041385
ER -