Resistance to immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer

Li, Yunchang; Hu, Lanlin; Peng, Xinhao; Xu, Huasheng; Tang, Bo; Xu, Chuan

doi:10.20517/cdr.2021.102

Cited by 8 publications

(12 citation statements)

References 152 publications

(283 reference statements)

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“…Their study raised the important role of circRNA in immune resistance and provided a potential targeted pathway "hsa_circ_0020714/miR-30a-5p/SOX4" to overcome resistance to anti-PD-1 therapy. The role of tumor-derived exosomes in tumor response to immunotherapy was recapitulated by Wu et al, and they pointed out that tumor-derived exosomes should be studied and manipulated to provide clinical benefits and improve the clinical management of lung cancer [39] . Li et al reviewed the resistance mechanism to ICIs, especially in KRAS-mutant NSCLC, with a critical focus on metabolism remodeling mediated by the oncogenic KRAS pathway, and they argued that these alternated metabolic pathways could be promising approaches to overcome immunotherapy resistance [40] .…”

Section: Resistance Mechanism For Icis-based Therapymentioning

confidence: 99%

“…Li et al . reviewed the resistance mechanism to ICIs, especially in KRAS-mutant NSCLC, with a critical focus on metabolism remodeling mediated by the oncogenic KRAS pathway, and they argued that these alternated metabolic pathways could be promising approaches to overcome immunotherapy resistance [ 40 ] . From the present clinical practice, Yu et al .…”

Section: Main Textmentioning

confidence: 99%

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Emerging insights to lung cancer drug resistance

Su¹

2022

Cancer Drug Resist

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Lung cancer remains the malignant tumor with the highest morbidity and mortality in China, with non-small cell lung cancer (NSCLC) accounting for 80%-85% of cases. Nowadays, the treatment pattern of NSCLC has evolved toward precision management with the development of molecular targeted therapy and immunotherapy. However, the median overall survival for patients with metastatic NSCLC, unfortunately, remains less than three years. Drug resistance is the bottleneck to preventing drugs from playing a further role, and the mechanistic study of drug resistance is the prerequisite for new regimen development. This Special Issue pays special attention to drug resistance in the treatment of NSCLC. We received and published several excellent articles regarding this topic. We hope that, through this Special Issue, we can have a deep understanding of the existing problems, the underlying mechanism, and the future solutions and that the publication of this Special Issue can bring some inspiration to readers.

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Section: Resistance Mechanism For Icis-based Therapymentioning

confidence: 99%

Section: Main Textmentioning

confidence: 99%

Emerging insights to lung cancer drug resistance

Su¹

2022

Cancer Drug Resist

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“…Mice with genetic loss of Nocth1 or Nocth2 facilitated SCLC tumorigenesis and formed non-neuroendocrine populations via regulation of RUNX2/REST pathway and STING (stimulator of interferon genes) ( Hong et al, 2022 ). Li Y. et al (2022) reported that Notch pathway was correlated with TIME in SCLC. Notch1 gene mutation was negatively linked to PD-L1 expression in SCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer

Wang

Zhu²,

Yang³

et al. 2023

Front. Pharmacol.

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Lung cancer is the common malignant tumor with the highest mortality rate. Lung cancer patients have achieved benefits from immunotherapy, including immune checkpoint inhibitors (ICIs) therapy. Unfortunately, cancer patients acquire adaptive immune resistance, leading to poor prognosis. Tumor microenvironment (TME) has been demonstrated to play a critical role in participating in acquired adaptive immune resistance. TME is associated with molecular heterogeneity of immunotherapy efficacy in lung cancer. In this article, we discuss how immune cell types of TME are correlated with immunotherapy in lung cancer. Moreover, we describe the efficacy of immunotherapy in driven gene mutations in lung cancer, including KRAS, TP53, EGFR, ALK, ROS1, KEAP1, ZFHX3, PTCH1, PAK7, UBE3A, TNF-α, NOTCH, LRP1B, FBXW7, and STK11. We also emphasize that modulation of immune cell types of TME could be a promising strategy for improving adaptive immune resistance in lung cancer.

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“…However, heterogeneity of immune checkpoint protein expression is a feature of NSCLC that limits the broad effectiveness of these therapies (Gettinger et al, 2015), with the absence of PD-L1 expression identified in both human and murine tumors with oncogenic KRAS and loss-of-function LKB1 mutations (Calles et al, 2015, Koyama et al, 2016, Skoulidis et al, 2015). The absence of checkpoint marker expression in pre-clinical models of dual KRAS; LKB1 mutated NSCLC corresponded with poor to no-responsiveness to checkpoint immunotherapy and subsequently effective treatments to durably target tumors that are non-responsive to immunotherapy or TKIs remain lacking (Skoulidis et al, 2018, Li et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Development of an adenosquamous carcinoma histopathology-selective lung cancer graft model

Lähdeniemi

Devlin

Nagaraj

et al. 2022

Preprint

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Preclinical tumor models with native tissue microenvironments provide essential tools to understand how heterogeneous tumor phenotypes relate to drug response. Here, we present syngeneic graft models of aggressive, metastasis-prone histopathology-specific NSCLC tumor types driven by KRAS mutation and loss of LKB1 (KL): adenosquamous carcinoma (ASC) and adenocarcinoma (AC). We show that subcutaneous injection of primary KL-ASC cells results in squamous cell carcinoma (SCC) tumors with high levels of stromal infiltrates, lacking the source heterogeneous histotype. Despite forming subcutaneous tumors, intravenously injected KL-AC cells were unable to form lung tumors. In contrast, intravenous injection of KL-ASC cells leads to their lung re-colonization and lesions recapitulating the mixed AC and SCC histopathology, tumor immune suppressive microenvironment and oncogenic signaling profile of source tumors, demonstrating histopathology-selective phenotypic dominance over genetic drivers. Pan-ERBB inhibition increased survival, while selective ERBB1/EGFR inhibition did not, suggesting a role of ERBB network crosstalk in resistance to ERBB1/EGFR. This immunocompetent NSCLC lung colonization model hence phenocopies key properties of the metastasis-prone ASC histopathology, and serves as a preclinical model to dissect therapy responses and metastasis-associated processes.

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Resistance to immune checkpoint inhibitors in KRAS-mutant non-small cell lung cancer

Cited by 8 publications

References 152 publications

Emerging insights to lung cancer drug resistance

Emerging insights to lung cancer drug resistance

Targeting immune cell types of tumor microenvironment to overcome resistance to PD-1/PD-L1 blockade in lung cancer

Development of an adenosquamous carcinoma histopathology-selective lung cancer graft model

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