Colorectal cancer spheroid biobanks: multi-level approaches to drug sensitivity studies

Cell Biology and Toxicology
Maria Laura De AngelisMarta Baiocchi

Abstract

Biobanking of molecularly characterized colorectal cancer stem cells (CSCs) generated from individual patients and growing as spheroids in defined serum-free media offer a fast, feasible, and multi-level approach for the screening of targeted therapies and drug resistance molecular studies. By combining in vitro and in vivo analyses of cetuximab efficacy with genetic data on an ongoing collection of stem cell-enriched spheroids, we describe the identification and preliminary characterization of microsatellite stable (MSS) CSCs that, despite the presence of the KRAS (G12D) mutation, display epidermal growth factor (EGF)-dependent growth and are strongly inhibited by anti-EGF-receptor (EGFR) treatment. In parallel, we detected an increased resistance to anti-EGFR therapy of microsatellite instable (MSI) CSC lines irrespective of KRAS mutational status. MSI CSC lines carried mutations in genes coding for proteins with a role in RAS and calcium signaling, highlighting the role of a genomically unstable context in determining anti-EGFR resistance. Altogether, these results argue for a multifactorial origin of anti-EGFR resistance that emerges as the effect of multiple events targeting direct and indirect regulators of the EGFR pathw...Continue Reading

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Citations

Sep 12, 2019·BioImpacts : BI·Mostafa Akbarzadeh KhiaviMohammad Hossein Somi
Sep 30, 2019·Cellular and Molecular Life Sciences : CMLS·Mostafa Akbarzadeh KhiaviYadollah Omidi
Nov 28, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Xiao ZhuHui Luo
Apr 30, 2021·Frontiers in Bioengineering and Biotechnology·Judith PapeUmber Cheema

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Methods Mentioned

BETA
xenografting
exome sequencing
xenograft
PCR
electrophoresis
genotyping
xenografts
Assay
nucleotide exchange
dissection

Software Mentioned

Sequencing Analysis
GeneMapper
GraphPad Prism
Mutect
SnpEff
GATK
Image Lab
BWA

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