# Editorial: Developing next-generation therapeutics to defeat mutation-driven cancer

Frances Chow, François Lamoureux, Gatien Moriceau

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Frances Chow, François Lamoureux, Gatien Moriceau. Editorial: Developing next-generation therapeutics to defeat mutation-driven cancer. Frontiers in Immunology, 2024, 15, 10.3389/fimmu.2024.1487952. [hal-05130822](https:// HAL Id: hal-05130822 )

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Submitted on 26 Jun 2025

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OPEN ACCESS

EDITED AND REVIEWED BY
Peter Brossart,
University of Bonn, Germany

*CORRESPONDENCE
Gatien Moriceau

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g moriceau@mednet.ucla.edu

RECEIVED 29 August 2024

ACCEPTED 11 September 2024

PUBLISHED 26 September 2024

CITATION

Chow F, Lamoureux F and
Moriceau G (2024) Editorial:
Developing next-generation
therapeutics to defeat
mutation-driven cancer.
Front. Immunol. 15:1487952.
doi: 10.3389/fimmu.2024.1487952

COPYRIGHT

© 2024 Chow, Lamoureux and Moriceau. This
is an open-access article distributed under the
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provided the original author(s) and the
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original publication in this journal is cited, in
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Editorial: Developing
next-generation therapeutics
to defeat mutation-driven cancer

Frances Chow<fnref n="1" />, François Lamoureux<fnref n="2" /> and Gatien Moriceau³*

KEYWORDS

next generation therapeutics, immunotherapy, antibody drug conjugate (ADC), targeted therapy, drug resistance, combination therapy, cancer

Editorial on the Research Topic

Developing next-generation therapeutics to defeat mutation-driven cancer

Mutation-driven cancers are one of the major medical challenges of the current century. Over the past decade, intense comprehensive sequencing has revealed the genomic, transcriptomic, and epigenetic landscapes in cancer, leading to the investigation of novel tailored therapeutic approaches. Mutation-induced hyperactivated signaling plays a significant role in cancer and has risen to recognition as a potential druggable target via the exploitation of cancer cell vulnerabilities. Despite revolutionary advances in immunotherapies and targeted therapies, innate and acquired resistance develop nearly universally, highlighting the need for ongoing research in innovative therapeutic strategies to defeat mutation-driven cancers.

The aim of the present Research Topic is to feature: (i) preclinical proof of concept studies to support well-defined single or combination regimens, (ii) target-based mechanisms that lend themselves to combination therapies by conserving or boosting immune responses, and (iii) approaches to overcome acquired resistance to current therapies.

As editors of this Research Topic, we had the pleasure of reading highly innovative manuscripts. We summarize the main findings and perspectives of each accepted manuscript in this editorial. This Research Topic features one original research manuscript and three reviews.

The original research manuscript by *Yang et al.* explores the possibility of predicting pancreatic ductal adenocarcinoma (PDAC) prognosis based on KRAS mutation status. They combined a multi-omics approach using two different cohorts to stratify overall survival risk and identify key components of ferroptosis-associated pathways as potential druggable targets. Their model lays the foundation for next-generation therapeutic strategies against PDAC.

The review by *Song et al.* comprehensively and concisely describes the potential role of the transcription factor AP-1, which they propose may offer a multi-pronged attack against cancer by enhancing targeted- and immune-based approaches. In addition to regulating the

<footnote n="1">¹Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, United States,</footnote>

<footnote n="2">²CRCI2NA/INSERM UMR 1307/CNRS UMR 6075/Nantes Université, Nantes, France, ³Division of Dermatology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States</footnote>
transcription of downstream target genes, AP-1 targeted inhibition
can reduce immune checkpoint expression, overcome CAR-T cell
exhaustion, overcome resistance to HDAC targeted therapy, and
sensitize to PARP1, CDK4/6 and EGFR targeted therapy.

The review by Hsu et al. offers insight into the exploration of antibody-drug conjugates (ADCs) for MET, HER3, EGFR, Trop2, and other targets in EGFR-mutated non-small cell lung cancer (NSCLC). The first EGFR-targeted drug approved by the FDA in 2013, osimertinib, a third-generation tyrosine kinase inhibitor, is now used for advanced NSCLC. However, resistance to osimertinib occurs, leading to consideration of ADCs as new therapeutic strategy. The authors describe therapeutic perspectives that could overcome resistance and present several key clinical trials which may extend this promising therapeutic approach to malignancies beyond NSCLC.

The review by Benjamin et al. elegantly presents the evolution of FGFR-targeting therapy clinical trials for metastatic urothelial carcinoma. The lessons learned from these trials of monotherapy erdafitinib, the combination of erdafitinib plus chemotherapy, and the combination of erdafitinib plus immunotherapy help to inform ongoing and future planned clinical trials of FGFR-targeting therapies. The authors propose unique approaches to overcome acquired resistance by targeting the PI3K pathway, the V561M mutation within the FGFR1 tyrosine kinase domain, and the EGFR pathway.

The guest Editors would like to thank all authors for
contributing their highly stimulating results in this topic and all

the Reviewers for giving their time to make this Research
Topic possible.

Author contributions

FC: Conceptualization, Writing – original draft, Writing – review & editing. FL: Conceptualization, Writing – original draft, Writing – review & editing. GM: Conceptualization, Project administration, Supervision, Writing – original draft, Writing – review & editing.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.