Non-small-cell lung cancer articles within Nature Communications

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• Article
  08 June 2024 | Open Access

  Tobacco-induced hyperglycemia promotes lung cancer progression via cancer cell-macrophage interaction through paracrine IGF2/IR/NPM1-driven PD-L1 expression

  Tobacco smoking is an important risk factor for lung cancer. Here the authors report that tobacco carcinogens promote metabolic syndrome and metabolic reprogramming of macrophages, associated with lung cancer progression in preclinical models.

  • Hyun-Ji Jang
  • , Hye-Young Min
  •  & Ho-Young Lee

• Article
  03 June 2024 | Open Access

  PPIA dictates NRF2 stability to promote lung cancer progression

  Despite being an established oncogenic driver of non-small cell lung cancer (NSCLC), therapies targeting NRF2 hyperactivation are lacking. Here, the authors identify peptidylprolyl isomerase A (PPIA) as a mediator of NRF2 stability and demonstrate the efficacy of targeting this interaction with cyclosporin A in preclinical models of NSCLC.

  • Weiqiang Lu
  • , Jiayan Cui
  •  & Jin Huang

• Article
  31 May 2024 | Open Access

  Representation of genomic intratumor heterogeneity in multi-region non-small cell lung cancer patient-derived xenograft models

  Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

  • Robert E. Hynds
  • , Ariana Huebner
  •  & Charles Swanton

• Article
  31 May 2024 | Open Access

  The thioredoxin system determines CHK1 inhibitor sensitivity via redox-mediated regulation of ribonucleotide reductase activity

  The clinical application of inhibitors targeting checkpoint kinase 1 (CHK1) is challenged by limited efficacy. Here, the authors identify that thioredoxin (Trx) system inhibition mediates sensitivity to CHK1 inhibitor via regulating the activity of ribonucleotide reductase, demonstrating the synergistic effect of CHK1 inhibitor and inhibitors targeting Trx system in lung cancer models.

  • Chandra Bhushan Prasad
  • , Adrian Oo
  •  & Junran Zhang

• Article
  23 May 2024 | Open Access

  Single-cell and spatial transcriptomics analysis of non-small cell lung cancer

  Myeloid cell populations play a critical role in lung cancer progression. Here, the authors use scRNA-seq and spatial transcriptomics to identify changes in the phenotype of macrophages within the tumour microenvironment.

  • Marco De Zuani
  • , Haoliang Xue
  •  & Ana Cvejic

• Article
  18 May 2024 | Open Access

  Mitochondrial respiratory function is preserved under cysteine starvation via glutathione catabolism in NSCLC

  The relevance of mitochondrial cysteine metabolism to ferroptosis is unknown. Here, Ward et al. show that mitochondrial Fe-S cluster synthesis persists under cysteine limitation via the catabolism of glutathione and at the expense of cell viability.

  • Nathan P. Ward
  • , Sang Jun Yoon
  •  & Gina M. DeNicola

• Article
  17 May 2024 | Open Access

  Ferritinophagy mediates adaptive resistance to EGFR tyrosine kinase inhibitors in non-small cell lung cancer

  The mechanisms leading to acquired resistance to targeted therapy in cancer are not completely understood. Here, the authors show that ferritinophagy mediates adaptive resistance to Osimertinib, and that combining this EGFR tyrosine kinase inhibitor with copper ionophores improves its therapeutic efficacy in preclinical models of non-small cell lung cancer.

  • Hui Wang
  • , Qianfan Hu
  •  & Feng Jiang

• Article
  03 May 2024 | Open Access

  Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer

  Remaining drug-tolerant persistent (DTP) cancer cells limit the efficacy of targeted therapy in EGFR, ALK and KRAS mutant non-small cell lung cancer (NSCLC). Here, the authors show that focal adhesion kinase (FAK)-YAP signalling supports DTP cells promoting residual disease and targeting this pathway improved tumour response in NSCLC preclinical models.

  • Franziska Haderk
  • , Yu-Ting Chou
  •  & Trever G. Bivona

• Article
  11 April 2024 | Open Access

  Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights

  Predicting recurrence risk in non small cell lung cancer can help to guide treatment decisions. Here, the authors use CT and PET imaging to develop predictive imaging subtypes, which can be integrated with existing ctDNA methods to predict recurrence.

  • Sheeba J. Sujit
  • , Muhammad Aminu
  •  & Jia Wu

• Article
  28 March 2024 | Open Access

  Comprehensive mutational scanning of EGFR reveals TKI sensitivities of extracellular domain mutants

  EGFR mutations are frequent in glioblastoma and lung cancer. Here, the authors perform deep mutational scanning of EGFR, followed by a high-throughput functional screen and analysis of patient data, to identify variants with differing sensitivities to a range of EGFR tyrosine kinase inhibitors.

  • Tikvah K. Hayes
  • , Elisa Aquilanti
  •  & Matthew Meyerson

• Article
  26 March 2024 | Open Access

  Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis

  Colitis is one of the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors. Here the authors show that a polygenic risk score for ulcerative colitis can predict immune checkpoint inhibitor-mediated colitis in patients with cancer.

  • Pooja Middha
  • , Rohit Thummalapalli
  •  & Elad Ziv

• Article
  23 March 2024 | Open Access

  Outcome differences by sex in oncology clinical trials

  The role of sex differences in response to cancer therapy remains unclear but this could be improved by reporting sex comparisons of outcomes in clinical trials. Here, the authors characterise the sex outcome comparisons in 89,221 interventional trials, finding that while comparisons were rare, important insights could be obtained.

  • Ashwin V. Kammula
  • , Alejandro A. Schäffer
  •  & Eytan Ruppin

• Article
  22 March 2024 | Open Access

  BET inhibitors drive Natural Killer activation in non-small cell lung cancer via BRD4 and SMAD3

  Combination of BET inhibitors (BETi) with immunotherapy has been reported to be synergic for the treatment of non-small cell lung carcinoma (NSCLC). Here, the authors show that BETi-induced epigenetic reprogramming downregulates the expression of NK cell inhibitory receptors on NK cells, increasing their activation and cytotoxicity against NSCLC.

  • Francesca Reggiani
  • , Giovanna Talarico
  •  & Valentina Sancisi

• Article
  21 March 2024 | Open Access

  GAS41 modulates ferroptosis by anchoring NRF2 on chromatin

  GAS41 is recognized as a histone reader and oncogene, but the mechanism by which GAS41 contributes to tumorigenesis is not well understood. Here, the authors discover that GAS41 is a ferroptosis repressor that anchors NRF2 to chromatin, promoting tumor growth.

  • Zhe Wang
  • , Xin Yang
  •  & Wei Gu

• Article
  19 March 2024 | Open Access

  Drug-resistant EGFR mutations promote lung cancer by stabilizing interfaces in ligand-free kinase-active EGFR oligomers

  The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Here, the authors show that EGFR lung cancer mutations promote the assembly of kinase-active dimers within ligand-free EGFR oligomers. These dimers bind ligand with high affinity and promote tumor growth.

  • R. Sumanth Iyer
  • , Sarah R. Needham
  •  & Marisa L. Martin-Fernandez

• Article
  28 February 2024 | Open Access

  A Phase II trial of alternating osimertinib and gefitinib therapy in advanced EGFR-T790M positive non-small cell lung cancer: OSCILLATE

  Alterations of therapeutic pressures have been shown to affect clonal evolution of resistance. Here, the authors conducted a single arm, phase 2 trial consisting of alternating osimertinib and gefitinib in non-small cell lung cancer, and found ctDNA dynamics were predictive of response.

  • Lavinia Tan
  • , Chris Brown
  •  & Benjamin J. Solomon

• Article
  19 February 2024 | Open Access

  Sintilimab with two cycles of chemotherapy for the treatment of advanced squamous non-small cell lung cancer: a phase 2 clinical trial

  Combining standard 4-6 cycles of chemotherapy with immune checkpoints inhibitors has shown to improve survival in patients with non-small cell lung cancer (NSCLC), however increased toxicities have also been reported. Here the authors report the results of a phase 2 trial of sintilimab (anti-PD1) with two cycles of chemotherapy for treatment of previously untreated advanced squamous NSCLC.

  • Mina Zhang
  • , Guowei Zhang
  •  & Huijuan Wang

• Article
  19 December 2023 | Open Access

  Neoadjuvant durvalumab plus radiation versus durvalumab alone in stages I–III non-small cell lung cancer: survival outcomes and molecular correlates of a randomized phase II trial

  The authors previously reported the primary outcomes of a randomized phase II trial comparing neoadjuvant durvalumab (anti-PD-L1) alone or in combination with stereotactic radiotherapy in patients with early-stage NSCLC. Here, the authors report the secondary outcomes of the trial and post hoc analysis.

  • Nasser K. Altorki
  • , Zachary H. Walsh
  •  & Timothy E. McGraw

• Article
  15 December 2023 | Open Access

  Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma

  Current sequencing technologies can shed light on the stepwise progression of lung adenocarcinoma. Here, the authors characterize tumor progression in lung adenocarcinomas from an early stage using short and long read whole-genome sequencing, bulk and spatial transcriptomics, and epigenomics.

  • Yasuhiko Haga
  • , Yoshitaka Sakamoto
  •  & Ayako Suzuki

• Article
  11 November 2023 | Open Access

  Dostarlimab or pembrolizumab plus chemotherapy in previously untreated metastatic non-squamous non-small cell lung cancer: the randomized PERLA phase II trial

  Several PD-(L)1 inhibitors have been approved or are in development for the treatment of NSCLC, showing promising efficacy and tolerable safety profiles. Here, the authors present a randomized phase II clinical trial comparing two different anti-PD-1 antibodies, dostarlimab and pembrolizumab, both combined with chemotherapy as first-line treatment in patients with metastatic NSCLC.

  • Sun Min Lim
  • , Solange Peters
  •  & Filippo de Marinis

• Article
  08 November 2023 | Open Access

  Inflammation in the tumor-adjacent lung as a predictor of clinical outcome in lung adenocarcinoma

  Lung adenocarcinoma is often curable when diagnosed at an early stage, but a subsection of patients will progress. Here, the authors use multi-omics profiling to show that gene expression data can predict clinical outcome.

  • Igor Dolgalev
  • , Hua Zhou
  •  & Aristotelis Tsirigos

• Article
  03 November 2023 | Open Access

  Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma

  Chemo-activation of mitochondrial ClpP exhibits promising anticancer properties. Here, the authors develop a potent activator ZK53 that is highly selective on human ClpP but inactive toward bacterial ClpP proteins, and show that ZK53 causes cell cycle arrest via ClpP on lung squamous cell carcinoma cells and exhibits therapeutic effects in animal models.

  • Lin-Lin Zhou
  • , Tao Zhang
  •  & Cai-Guang Yang

• Article
  20 September 2023 | Open Access

  Critical requirement of SOS1 for tumor development and microenvironment modulation in KRAS^G12D-driven lung adenocarcinoma

  Critical regulators of RAS signaling pathways in oncogenic RAS-driven tumors remain to be explored. Here, the authors show the development of KRAS(G12D)-driven lung adenocarcinoma is dependent on SOS1, with dual roles in both tumor and stroma.

  • Fernando C. Baltanás
  • , Rósula García-Navas
  •  & Eugenio Santos

• Article
  02 September 2023 | Open Access

  Atezolizumab plus stereotactic ablative radiotherapy for medically inoperable patients with early-stage non-small cell lung cancer: a multi-institutional phase I trial

  Stereotactic ablative radiotherapy (SABR) is standard-of-care for patients with medically inoperable early-stage non-small cell lung cancer (NSCLC), however the risk of systemic recurrences remains high. Here the authors report the results of a phase I study testing the addition of atezolizumab (anti-PD-L1) to SABR in high risk, medically inoperable, early-stage, NSCLC.

  • Arta M. Monjazeb
  • , Megan E. Daly
  •  & Karen Kelly

• Article
  22 August 2023 | Open Access

  Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy

  Immune checkpoint blockade therapy improved the survival rates of non-small cell lung cancer but only a proportion of patients benefit. Here authors follow the humoral and cellular immunological parameters of patients undergoing anti-PD1 therapy longitudinally and find that levels and functional properties of cytotoxic T cells, and especially CD8⁺CD101^hiTIM3⁺ cells determine the response.

  • Elaine Lai-Han Leung
  • , Run-Ze Li
  •  & Liang Liu

• Article
  17 August 2023 | Open Access

  Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis

  The genomic landscape of brain metastasis (BM) in patients with non-small cell lung cancer (NSCLC) remains to be explored. Here, the authors analyse a cohort of 233 patients with BM including 47 primary tumour, 42 extracranial metastatic matched samples and reveal distinct mutational patterns.

  • Anna Skakodub
  • , Henry Walch
  •  & Luke R. G. Pike

• Article
  03 August 2023 | Open Access

  Neoadjuvant Afatinib for stage III EGFR-mutant non-small cell lung cancer: a phase II study

  Afatinib is a second-generation EGFR tyrosine kinase inhibitor recommended as the first-line treatment for patients with advanced EGFR mutant non-small cell lung cancer (NSCLC). Here the authors report the results of a phase II clinical trial of neoadjuvant afatinib for stage III EGFR mutant NSCLC.

  • Dongliang Bian
  • , Liangdong Sun
  •  & Peng Zhang

• Article
  15 July 2023 | Open Access

  Impact of TMB/PD-L1 expression and pneumonitis on chemoradiation and durvalumab response in stage III NSCLC

  Concurrent chemoradiation and durvalumab is standard of care for stage III non-small cell lung cancer, however, efficacy is variable. Here, the authors show PD-L1 tumor proportion score expression and increased tumor mutational burden are predictive of response and that early-onset pneumonitis leading to durvalumab discontinuation is associated with poor survival.

  • Joao V. Alessi
  • , Biagio Ricciuti
  •  & Narek Shaverdian

• Article
  05 July 2023 | Open Access

  UHRF1 is a mediator of KRAS driven oncogenesis in lung adenocarcinoma

  Identifying KRAS-specific vulnerabilities helps to target KRAS-driven cancer. Here the authors perform RNA interference screens in 3D cultures of primary tumour cells with KRAS activation and p53 loss and identify UHRF1 as a vulnerability of KRAS-mutant lung cancers

  • Kaja Kostyrko
  • , Marta Román
  •  & E. Alejandro Sweet-Cordero

• Article
  28 June 2023 | Open Access

  A landscape of response to drug combinations in non-small cell lung cancer

  Combination of drugs within cancer treatment is a popular way to overcome resistance and increase efficacy. Here, the authors analyse over 5000 targeted agent combinations in non-small cell lung cancer to identify potentially effective drug strategies.

  • Nishanth Ulhas Nair
  • , Patricia Greninger
  •  & Cyril H. Benes

• Article
  12 June 2023 | Open Access

  Phase 1b trial of anti-EGFR antibody JMT101 and Osimertinib in EGFR exon 20 insertion-positive non-small-cell lung cancer

  Patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertions are resistant to early generation EGFR tyrosine kinase inhibitors (TKI). Here, the authors report the safety and preliminary efficacy of a phase I clinical trial JMT101, an anti-EGFR antibody, combined with EGFR-TKI, afatinib or osimertinib, in patients with NSCLC.

  • Shen Zhao
  • , Wu Zhuang
  •  & Wenfeng Fang

• Article
  02 June 2023 | Open Access

  NOTCH4^ΔL12_16 sensitizes lung adenocarcinomas to EGFR-TKIs through transcriptional down-regulation of HES1

  Patients with lung adenocarcinoma (LUAD) patients carrying EGFR mutations are often treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs), but sensitivity to the therapy varies. Here, using 3D printed patient derived xenograft models, the authors identify a NOTCH mutation as an indicator of favourable response to EGFR-TKI in LUAD.

  • Bin Zhang
  • , Shaowei Dong
  •  & Chang Zou

• Article
  01 June 2023 | Open Access

  The blood proteome of imminent lung cancer diagnosis

  Lung cancer screening could enhance early diagnosis and treatment. Here, the authors used proteomic analysis of pre-diagnosis samples across 6 cohorts to identify 36 proteins associated with imminent lung cancer diagnosis.

  • Demetrius Albanes
  • , Karine Alcala
  •  & Wei Zheng

• Article
  31 May 2023 | Open Access

  In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy response in lung cancer

  There is still a limited understanding of mechanisms of sensitivity/resistance to cancer immunotherapy. Here the authors perform in vivo CRISPR/Cas9 loss-of-function screens in mouse lung cancer models, revealing Serpinb9 and Adam2 as regulators of immunotherapy response.

  • Dzana Dervovic
  • , Ahmad A. Malik
  •  & Daniel Schramek

• Article
  25 April 2023 | Open Access

  Immune cellular patterns of distribution affect outcomes of patients with non-small cell lung cancer

  The spatial distribution of cellular compartments within the tumour microenvironment in non-small cell lung cancer (NSCLC) remains to be investigated. Here, the authors identify distinct cell populations of tumour cells and tumour-associated immune cell phenotypes with different spatial distributions in NSCLC.

  • Edwin Roger Parra
  • , Jiexin Zhang
  •  & Ignacio Ivan Wistuba

• Article
  04 March 2023 | Open Access

  CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy

  LKB1 mutations have been associated with primary resistance to immune checkpoint inhibitors in patients with lung cancer. Here the authors show that Lkb1-deficient lung tumors are characterized by defective trafficking and adhesion of T cells and that, by upregulating ICAM1 expression, CDK4/6 inhibitors sensitize LKB1 mutant lung cancer to anti-PD1 blockade.

  • Xue Bai
  • , Ze-Qin Guo
  •  & Zhong-Yi Dong

• Article
  08 February 2023 | Open Access

  Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

  Immune checkpoint inhibitors with or without chemotherapy are now standard of care for non-small cell lung cancer. However, the benefits of combination vs sequential therapy have not been fully explored. Here, the authors analysed 1,133 patient records and show combination therapy showed increased protection against early progression, but similar overall survival.

  • Lingzhi Hong
  • , Muhammad Aminu
  •  & Natalie I. Vokes

• Article
  31 January 2023 | Open Access

  Single-cell analysis reveals prognostic fibroblast subpopulations linked to molecular and immunological subtypes of lung cancer

  Fibroblast heterogeneity is a prominent but poorly understood feature of solid tumours. Here three major fibroblast subpopulations in non-small cell lung cancer are identified and characterised through single cell RNA-sequencing, multiplexed immunohistochemistry and digital cytometry.

  • Christopher J. Hanley
  • , Sara Waise
  •  & Gareth J. Thomas

• Article
  09 January 2023 | Open Access

  Tumor-intrinsic IRE1α signaling controls protective immunity in lung cancer

  The IRE1α-XBP1 arm of the unfolded protein response (UPR) has been associated with immunosuppression and cancer progression. Here the authors show that IRE1α-XBP1 activation is associated with poor overall survival in patients with non-small cell lung cancer and that IRE1α loss in cancer cells promotes anti-tumor immune responses in lung cancer preclinical models.

  • Michael J. P. Crowley
  • , Bhavneet Bhinder
  •  & Vivek Mittal

• Article
  17 December 2022 | Open Access

  USP5-Beclin 1 axis overrides p53-dependent senescence and drives Kras-induced tumorigenicity

  Oncogene-induced senescence (OIS) occurs in premalignant lung adenomas, but infrequently in malignant adenocarcinomas. Here the authors show that USP5-Beclin 1 axis overcomes OIS in Kras-driven lung cancer by enhancing MDM2-mediated p53 degradation.

  • Juan Li
  • , Yang Wang
  •  & Zhi-Xiong Jim Xiao

• Article
  14 November 2022 | Open Access

  A fluorogenic probe for predicting treatment response in non-small cell lung cancer with EGFR-activating mutations

  The presence of activating epidermal growth factor receptor (EGFR) mutations in patients with lung cancer correlates to improved response to EGFR-tyrosine kinase inhibitors. Here, the authors present a fluorescence-activated cell sorting assay to identify EGFR mutations with functional activity in patients and demonstrate its utility in predicting response to EGFR-TKI.

  • Hui Deng
  • , Qian Lei
  •  & Weimin Li

• Article
  10 November 2022 | Open Access

  Biochemical and structural basis for differential inhibitor sensitivity of EGFR with distinct exon 19 mutations

  Although small molecule tyrosine kinase inhibitors are effective in lung cancer driven by mutated EGFR, some receptor variants fail to respond. Here, the authors identify structural features of an important set of EGFR variants with reduced inhibitor sensitivity, guiding future inhibitor selection.

  • Iris K. van Alderwerelt van Rosenburgh
  • , David M. Lu
  •  & Yuko Tsutsui

• Article
  04 November 2022 | Open Access

  Tumor factors stimulate lysosomal degradation of tumor antigens and undermine their cross-presentation in lung cancer

  Dendritic cells (DC) present tumour antigens to T cells but this process is defective in the tumour microenvironment. Here the authors find that downregulation of cholesterol 25-hydroxylase underlies defective cross presentation of tumour antigens.

  • Zhen Lu
  • , Jinyun Chen
  •  & Serge Y. Fuchs

• Article
  19 October 2022 | Open Access

  Remodelling of tumour microenvironment by microwave ablation potentiates immunotherapy of AXL-specific CAR T cells against non-small cell lung cancer

  AXL is overexpressed and has been investigated as a therapeutic target in several cancer types, including lung cancer. Here the authors design AXLdirected CAR-T cells and show that their anti-tumor activity can be improved in combination with microwave ablation in preclinical lung cancer models.

  • Bihui Cao
  • , Manting Liu
  •  & Zhenfeng Zhang

• Article
  15 October 2022 | Open Access

  Phase I trial of the TNF-α inhibitor certolizumab plus chemotherapy in stage IV lung adenocarcinomas

  Generation of TNF-α in response to chemotherapy has been associated with chemo-resistance and metastasis propagation. Here the authors show that the combination of an anti-TNF antibody and cisplatin doublet chemotherapy increases anti-tumor efficacy in lung cancer preclinical models and report the results of a phase I clinical trial of the anti-TNF-α antibody certolizumab in combination with chemotherapy in patients with stage IV lung adenocarcinomas.

  • Paul K. Paik
  • , Jia Luo
  •  & Mark G. Kris

• Article
  14 October 2022 | Open Access

  Fibrocytes boost tumor-supportive phenotypic switches in the lung cancer niche via the endothelin system

  Fibrocytes are monocyte-derived cells implicated in wound healing. Here, the authors utilise single cell RNA-seq, genetic ablation and multiplexed imaging to identify a fibrocyte population in lung cancer models, and use human lung cancer coculture systems to highlight their potential to modulate microenvironmental niche and sensitivity to endothelin blockade.

  • Andreas Weigert
  • , Xiang Zheng
  •  & Rajkumar Savai

• Article
  10 October 2022 | Open Access

  The spatial transcriptomic landscape of non-small cell lung cancer brain metastasis

  Brain metastases (BrMs) in non-small cell lung cancer (NSCLC) are associated with dismal outcomes, and are possibly sustained by the brain microenvironment. Here, the authors analyse NSCLC BrMs using Digital Spatial Profiling and reveal fibrosis, immune suppression, and cell reprogramming in the BrM microenvironment.

  • Qi Zhang
  • , Rober Abdo
  •  & Shawn Shun-Cheng Li

• Article
  07 October 2022 | Open Access

  ZIP1⁺ fibroblasts protect lung cancer against chemotherapy via connexin-43 mediated intercellular Zn²⁺ transfer

  Cancer-associated fibroblasts (CAFs) have been implicated in lung cancer chemo-resistance. Here the authors show that a zinc-transporter positive CAF subset is enriched in lung cancer models after chemotherapy and actively transfers zinc to cancer cells, promoting ABCB1-mediated chemo-resistance.

  • Chen Ni
  • , Xiaohan Lou
  •  & Zhihai Qin

• Article
  26 September 2022 | Open Access

  RAS oncogenic activity predicts response to chemotherapy and outcome in lung adenocarcinoma

  Mutations in RAS oncogenes and related pathways are frequent in lung cancers. Here, the authors derive a RAS gene expression signature and a machine learning classifier to predict drug response and clinical outcomes in lung adenocarcinoma and other solid tumours, with improved performance over KRAS mutations alone.

  • Philip East
  • , Gavin P. Kelly
  •  & Sophie de Carné Trécesson

• Article
  24 September 2022 | Open Access

  Genomic and biological study of fusion genes as resistance mechanisms to EGFR inhibitors

  Fusion genes have been proposed as a potential mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in lung cancer. Here, the authors identify gene fusions that are associated with resistance to EGFR TKIs in non-small cell lung cancers, and test how these fusions impact the response to EGFR TKIs in vitro.

  • Yoshihisa Kobayashi
  • , Geoffrey R. Oxnard
  •  & Pasi A. Jänne