Have plastic culture models prevented the discovery of effective cancer therapeutics?

Br J Pharmacol

Cancer Metabolism and Microenvironment Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.

Published: November 2024

Conventional cell culture techniques generally fail to recapitulate the expression profiles or functional phenotypes of the in vivo equivalents they are meant to model. These cell culture models are indispensable for preclinical drug discovery and mechanistic studies. However, if our goal is to develop effective therapies that work as intended in the human body, we must revise our cell culture models to recapitulate normal and disease physiology to ensure that we identify compounds that are useful and effective beyond our in vitro models.

Download full-text PDF

Source
http://dx.doi.org/10.1111/bph.17387DOI Listing

Publication Analysis

Top Keywords

culture models
12
cell culture
12
plastic culture
4
models
4
models prevented
4
prevented discovery
4
discovery effective
4
effective cancer
4
cancer therapeutics?
4
therapeutics? conventional
4

Similar Publications

Despite the pivotal role of cytotoxic T lymphocytes (CTLs) in anti-tumor immunity, a substantial proportion of CTL-rich hepatocellular carcinoma (HCC) patients experience early relapse or immunotherapy resistance. However, spatial immune variations impacting the heterogeneous clinical outcomes of CTL-rich HCCs remain poorly understood. Here, we compared the single-cell and spatial landscapes of 20 CTL-rich HCCs with distinct prognoses using multiplexed in situ staining and validated the prognostic value of myeloid spatial patterns in a cohort of 386 patients.

View Article and Find Full Text PDF

Lineage Recording in Human Brain Organoids with iTracer.

Methods Mol Biol

January 2025

Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.

Induced pluripotent stem cell (iPSC)-derived organoids provide models to study human organ development. Single-cell transcriptomics enables highly resolved descriptions of cell states within these systems; however, approaches are needed to directly determine the lineage relationship between cells. Here we provide a detailed protocol (Fig.

View Article and Find Full Text PDF

The HOX and PBX genes encode transcription factors that have key roles in development and cancer, both independently and as a heterodimer within a complex of proteins that recognizes specific sequences in DNA and can both activate and repress transcription of target genes. Due to functional redundancy amongst HOX proteins, knock down or knock out studies of individual genes often do not result in an altered phenotype. An alternative approach is to target the interaction between HOX and PBX proteins, which is dependent on a conserved hexapeptide region within HOX.

View Article and Find Full Text PDF

Hox genes are highly conserved developmental regulators instrumental to the formation of a wide range of diverse body plans across metazoans. While significant progress in the field of Hox gene research has been made, persistent challenges in unraveling their mechanisms of action and full repertoire of functions remain. To date, investigations of Hox gene function have been primarily conducted in research models belonging to ecdysozoa and vertebrata.

View Article and Find Full Text PDF

Bimolecular Fluorescence Complementation (BiFC) is a powerful molecular imaging method used to visualize protein-protein interactions (PPIs) in living cells or organisms. BiFC is based on the reassociation of hemi-fragments of a monomeric fluorescent protein upon spatial proximity. It is compatible with conventional light microscopy, providing a resolution that is constrained by the diffraction of light to around 250 nm.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!