Cited by 311Cancer Immunotherapy and BiomarkersLung Cancer Treatments and MutationsCancer Cells and Metastasis

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Overcoming Resistance to Tumor-Targeted and Immune-Targeted Therapies

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Aldea, Mihaela, Andre, Fabrice, Marabelle, Aurelien, Dogan, Semih, Barlesi, Fabrice, Soria, Jean-Charles·2021·Cancer Discovery

DOI 10.1158/2159-8290.cd-20-1638

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Abstract

Resistance to anticancer therapies includes primary resistance, usually related to lack of target dependency or presence of additional targets, and secondary resistance, mostly driven by adaptation of the cancer cell to the selection pressure of treatment. Resistance to targeted therapy is frequently acquired, driven by on-target, bypass alterations, or cellular plasticity. Resistance to immunotherapy is often primary, orchestrated by sophisticated tumor–host–microenvironment interactions, but could also occur after initial efficacy, mostly when only partial responses are obtained. Here, we provide an overview of resistance to tumor and immune-targeted therapies and discuss challenges of overcoming resistance, and current and future directions of development. Significance: A better and earlier identification of cancer-resistance mechanisms could avoid the use of ineffective drugs in patients not responding to therapy and provide the rationale for the administration of personalized drug associations. A clear description of the molecular interplayers is a prerequisite to the development of novel and dedicated anticancer drugs. Finally, the implementation of such cancer molecular and immunologic explorations in prospective clinical trials could de-risk the demonstration of more effective anticancer strategies in randomized registration trials, and bring us closer to the promise of cure.

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Authors: Aldea, M., Andre, F., Marabelle, A., Dogan, S., Barlesi, F., & Soria, J.-C.
Affiliations: Institut Gustave Roussy (FR)
1Department of Medical Oncology, Gustave Roussy, Villejuif, France.
2INSERM U981, PRISM Institute, Gustave Roussy, Villejuif, France.
Université Paris-Saclay (FR)
Corresponding author: Soria, Jean-Charles
ORCID: Aldea, Mihaela
Andre, Fabrice
Marabelle, Aurelien
Dogan, Semih
Soria, Jean-Charles
Venue: Cancer Discovery
Publisher: American Association for Cancer Research (AACR)
Published: 2021-04-01
Volume: 11
Issue: 4
Pages: 874-899
ISSN: 2159-8274 (ISSN-L)
2159-8290
DOI: 10.1158/2159-8290.cd-20-1638
OpenAlex: W3142295235
Cited by: 311
References: 305
Citations by year: 2026: 47 · 2025: 93 · 2024: 67 · 2023: 46 · 2022: 40 · 2021: 17
FWCI: 5.21
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cancer Discovery (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Keywords: drug resistance, targeted therapy, immunotherapy, primary resistance, secondary resistance, bypass signaling, cellular plasticity, tumor microenvironment, personalized drug combinations, anticancer drug development
MeSH terms: Humans, Immunotherapy, Neoplasms, Drug Resistance, Neoplasm, Precision Medicine

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Overcoming Resistance to Tumor-Targeted and Immune-Targeted Therapies

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