Search research articles

ABOUT JoVE

Overview Leadership Blog JoVE Help Center

AUTHORS

Publishing Process Editorial Board Scope & Policies Peer Review FAQ Submit

LIBRARIANS

Testimonials Subscriptions Access Resources Library Advisory Board FAQ

RESEARCH

JoVE Journal Methods Collections JoVE Encyclopedia of Experiments Archive

EDUCATION

JoVE Core JoVE Business JoVE Science Education JoVE Lab Manual Faculty Resource Center Faculty Site

Terms & Conditions of Use

Related Concept Videos

Treatment Resistant Cancers

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by

Same author

Abnormal B-Cell Exosome Proapoptotic and Antiapoptotic Cargo in Multiple Sclerosis: Potential Implication in Progressive Disease Biology.

Neurology(R) neuroimmunology & neuroinflammation·2026

Same author

Erratum: Hepatectomy alters adjuvant anti-PD-1 action in a mouse model of HCC but does not compromise neoadjuvant efficacy.

Hepatology (Baltimore, Md.)·2026

Same author

[Digestive surgery : what's new in 2025].

Revue medicale suisse·2026

Same author

Risk of secondary appendiceal tumours after colorectal cancer surgery: nationwide Swiss registry study.

BJS open·2026

Same author

Efficacy of Immune Checkpoint Inhibitors and Oncoviruses in Solid Tumors.

Clinical cancer research : an official journal of the American Association for Cancer Research·2026

Same author

Emergence of high-metastatic potentials and prediction of recurrence and metastasis.

Cell reports·2025

Search research articles

Related Experiment Video

Updated: Aug 25, 2025

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells

Published on: January 22, 2021

FOLFOXIRI Resistance Induction and Characterization in Human Colorectal Cancer Cells.

George M Ramzy^1,2,3, Laura Boschung^1,2, Thibaud Koessler^3,4

¹Molecular Pharmacology Group, School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1211 Geneva, Switzerland.

|October 14, 2022

Summary

Chronic FOLFOXIRI treatment induces colorectal cancer (CRC) drug resistance. Optimized low-dose drug combinations overcome this resistance by targeting the Ras-Raf-MEK-ERK pathway and inhibiting cell metabolism.

Keywords:

FOLFOXIRI colorectal cancer drug-resistance

More Related Videos

Detection of Total Reactive Oxygen Species in Adherent Cells by 2',7'-Dichlorodihydrofluorescein Diacetate Staining

Detection of Total Reactive Oxygen Species in Adherent Cells by 2',7'-Dichlorodihydrofluorescein Diacetate Staining

Published on: June 23, 2020

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

Related Experiment Videos

Last Updated: Aug 25, 2025

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells

A Three-dimensional Model of Spheroids to Study Colon Cancer Stem Cells

Published on: January 22, 2021

Detection of Total Reactive Oxygen Species in Adherent Cells by 2',7'-Dichlorodihydrofluorescein Diacetate Staining

Detection of Total Reactive Oxygen Species in Adherent Cells by 2',7'-Dichlorodihydrofluorescein Diacetate Staining

Published on: June 23, 2020

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Immunofluorescence Imaging of DNA Damage and Repair Foci in Human Colon Cancer Cells

Published on: June 9, 2020

Area of Science:

Oncology
Pharmacology
Molecular Biology

Background:

FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin, irinotecan) is a standard first-line treatment for colorectal carcinoma (CRC).
Current FOLFOXIRI therapy is non-personalized and aggressive, potentially leading to acquired drug resistance in patients with advanced CRC.

Purpose of the Study:

To generate and characterize CRC cell clones with acquired resistance to chronic FOLFOXIRI treatment.
To investigate the molecular mechanisms underlying FOLFOXIRI resistance.
To identify novel therapeutic strategies to overcome acquired FOLFOXIRI resistance.

Main Methods:

Generation of CRC cell clones chronically exposed to FOLFOXIRI.
Assessment of drug sensitivity using 2D and 3D co-culture models.
Morphometric analysis of actin filament organization.
Bulk RNA sequencing to identify differentially expressed genes.
Evaluation of optimized low-dose synergistic drug combinations (ODCs).

Main Results:

Chronically treated CRC cell lines exhibited significant loss of sensitivity to FOLFOXIRI compared to treatment-naïve cells.
Acquired resistance was associated with changes in actin filament organization.
Resistant SW620 cells showed upregulation of glucose transporter family 5 (GLUT5).
Resistant LS174T cells displayed downregulation of protein tyrosine phosphatase receptor S (PTPRS) and oxoglutarate dehydrogenase-like gene (OGDHL).
Optimized low-dose synergistic drug combinations (ODCs) effectively overcame FOLFOXIRI resistance.
ODCs inhibited cell metabolic activity by up to 82% in resistant 3D co-cultures via the Ras-Raf-MEK-ERK pathway.

Conclusions:

Chronic FOLFOXIRI treatment leads to acquired drug resistance in colorectal cancer cells.
Specific gene expression changes (GLUT5, PTPRS, OGDHL) are implicated in FOLFOXIRI resistance.
Optimized low-dose synergistic drug combinations targeting the Ras-Raf-MEK-ERK pathway represent a promising strategy to overcome FOLFOXIRI resistance in advanced CRC.