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 Resistent Cancers

Treatment Resistent 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...

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...

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...

You might also read

Related Articles

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

Sort by

Same author

Nivolumab plus chemoradiotherapy followed by nivolumab with or without ipilimumab for untreated locally advanced stage III NSCLC: a randomized phase 3 trial.

Nature cancer·2026

Same author

Final Efficacy and Safety Data From the Phase I/II ARROW Study of Pralsetinib in Patients With Advanced <i>RET</i> Fusion-Positive Non-Small Cell Lung Cancer.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology·2026

Same author

Landscape of Genomic Mechanisms of Resistance to Selective RET Inhibitors in RET-Altered Solid Tumors: Analysis of the RETgistry Global Consortium.

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

Same author

Phase Ib Basket Expansion Trial and Alternative-Schedule Dose-Escalation Study of ATR Inhibitor Elimusertib in Advanced Solid Tumors with DNA Damage Response Defects.

Cancer discovery·2025

Same author

Zipalertinib in Patients With Epidermal Growth Factor Receptor Exon 20 Insertion-Positive Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy With or Without Amivantamab.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology·2025

Same author

The Impact of the Tumor Microenvironment on the Effect of IL-1β Blockade in NSCLC: Biomarker Analyses from CANOPY-1 and CANOPY-N Trials.

Cancer research communications·2025

Search research articles

Related Experiment Video

Updated: Jul 12, 2026

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

Rethinking Molecular Profiling Post First-Line Osimertinib.

Komal Gupta¹, Daniel S W Tan¹, Regina Hoo²

¹National Cancer Centre Singapore Singapore Singapore.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research

|July 10, 2026

Summary

The ORCHARD study reveals complex resistance mechanisms after first-line osimertinib treatment. Histo-genomic analysis found resistance alterations in 87% of patients, with 46% showing polyclonal resistance, impacting future treatment strategies.

More Related Videos

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Related Experiment Videos

Last Updated: Jul 12, 2026

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer

Ultra-Fast Amplicon-Based Next-Generation Sequencing in Non-Squamous Non-Small Cell Lung Cancer

Published on: September 8, 2023

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

Area of Science:

Oncology
Genomics
Pharmacology

Background:

First-line osimertinib is a standard treatment for EGFR-mutated non-small cell lung cancer.
Understanding resistance mechanisms is crucial for optimizing subsequent therapies.
The ORCHARD study provides the largest histo-genomic characterization of osimertinib resistance to date.

Purpose of the Study:

To comprehensively characterize resistance alterations following first-line osimertinib treatment.
To investigate the prevalence of polyclonal resistance mechanisms.
To inform the development of next-generation treatment strategies in the post-EGFR TKI setting.

Main Methods:

Dual-modality sequencing of both tissue and plasma samples.
Histo-genomic analysis of patient samples from the ORCHARD study.

Main Results:

Resistance alterations were detected in 87% of patients.
Polyclonal resistance mechanisms were identified in 46% of cases.
The findings highlight the complex biological landscape of post-osimertinib resistance.

Conclusions:

Osimertinib resistance is complex and frequently involves polyclonal mechanisms.
These findings raise important questions regarding the efficacy of targeted versus broadly acting regimens after EGFR TKI failure.
Further research is needed to guide optimal treatment sequencing.