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Journal Article

Modeling of Personalized Treatments in Colon Cancer Based on Preclinical Genomic and Drug Sensitivity Data

MPS-Authors
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Yaspo,  Marie-Laure
Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Lehrach,  Hans
Emeritus Group of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Keil et al_2021.pdf
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Citation

Keil, M., Conrad, T., Becker, M., Keilholz, U., Yaspo, M.-L., Lehrach, H., et al. (2021). Modeling of Personalized Treatments in Colon Cancer Based on Preclinical Genomic and Drug Sensitivity Data. cancers, 13(23): 6018. doi:10.3390/cancers13236018.


Cite as: https://hdl.handle.net/21.11116/0000-0009-BFAB-0
Abstract
The current standard therapies for advanced, recurrent or metastatic colon cancer are the
5-fluorouracil and oxaliplatin or irinotecan schedules (FOxFI) +/− targeted drugs cetuximab or
bevacizumab. Treatment with the FOxFI cytotoxic chemotherapy regimens causes significant toxicity
and might induce secondary cancers. The overall low efficacy of the targeted drugs seen in colon
cancer patients still is hindering the substitution of the chemotherapy. The ONCOTRACK project
developed a strategy to identify predictive biomarkers based on a systems biology approach, using
omics technologies to identify signatures for personalized treatment based on single drug response
data. Here, we describe a follow-up project focusing on target-specific drug combinations. Back-
ground for this experimental preclinical study was that, by analyzing the tumor growth inhibition in
the PDX models by cetuximab treatment, a broad heterogenic response from complete regression
to tumor growth stimulation was observed. To provide confirmation of the hypothesis that drug
combinations blocking alternatively activated oncogenic pathways may improve therapy outcomes,
25 models out of the well-characterized ONCOTRACK PDX panel were subjected to treatment with
a drug combination scheme using four approved, targeted cancer drugs.