TY - JOUR
T1 - Harnessing the predictive power of preclinical models for oncology drug development
AU - Honkala, Alexander
AU - Malhotra, Sanjay V.
AU - Kummar, Shivaani
AU - Junttila, Melissa R.
N1 - Funding Information:
The authors dedicate this work to the memory of Dr Georgia Hatzivassiliou. They also express gratitude to clinical trial patients and their families for their selfless contributions to research that is crucial for translation research and paves the way for improved patient treatments.
Publisher Copyright:
© 2021, Springer Nature Limited.
PY - 2022/2
Y1 - 2022/2
N2 - Recent progress in understanding the molecular basis of cellular processes, identification of promising therapeutic targets and evolution of the regulatory landscape makes this an exciting and unprecedented time to be in the field of oncology drug development. However, high costs, long development timelines and steep rates of attrition continue to afflict the drug development process. Lack of predictive preclinical models is considered one of the key reasons for the high rate of attrition in oncology. Generating meaningful and predictive results preclinically requires a firm grasp of the relevant biological questions and alignment of the model systems that mirror the patient context. In doing so, the ability to conduct both forward translation, the process of implementing basic research discoveries into practice, as well as reverse translation, the process of elucidating the mechanistic basis of clinical observations, greatly enhances our ability to develop effective anticancer treatments. In this Review, we outline issues in preclinical-to-clinical translatability of molecularly targeted cancer therapies, present concepts and examples of successful reverse translation, and highlight the need to better align tumour biology in patients with preclinical model systems including tracking of strengths and weaknesses of preclinical models throughout programme development.
AB - Recent progress in understanding the molecular basis of cellular processes, identification of promising therapeutic targets and evolution of the regulatory landscape makes this an exciting and unprecedented time to be in the field of oncology drug development. However, high costs, long development timelines and steep rates of attrition continue to afflict the drug development process. Lack of predictive preclinical models is considered one of the key reasons for the high rate of attrition in oncology. Generating meaningful and predictive results preclinically requires a firm grasp of the relevant biological questions and alignment of the model systems that mirror the patient context. In doing so, the ability to conduct both forward translation, the process of implementing basic research discoveries into practice, as well as reverse translation, the process of elucidating the mechanistic basis of clinical observations, greatly enhances our ability to develop effective anticancer treatments. In this Review, we outline issues in preclinical-to-clinical translatability of molecularly targeted cancer therapies, present concepts and examples of successful reverse translation, and highlight the need to better align tumour biology in patients with preclinical model systems including tracking of strengths and weaknesses of preclinical models throughout programme development.
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U2 - 10.1038/s41573-021-00301-6
DO - 10.1038/s41573-021-00301-6
M3 - Review article
C2 - 34702990
AN - SCOPUS:85118142129
VL - 21
SP - 99
EP - 114
JO - Nature Reviews Drug Discovery
JF - Nature Reviews Drug Discovery
SN - 1474-1776
IS - 2
ER -