LKB1 Expression Correlates with Increased Survival in Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy and Bevacizumab

Bonanno, Laura; De Paoli, Angela; Zulato, Elisabetta; Esposito, Giovanni; Calabrese, Fiorella; Favaretto, Adolfo; Santo, Antonio; Conte, Alessandro Del; Chilosi, Marco; Oniga, Francesco; Sozzi, Gabriella; Moro, Massimo; Ciccarese, Francesco; Nardo, Giorgia; Bertorelle, Roberta; Candiotto, Cinzia; De Salvo, Gian Luca; Amadori, Alberto; Conte, PierFranco; Indraccolo, Stefano

doi:10.1158/1078-0432.ccr-16-2410

Cited by 53Lung Cancer Treatments and MutationsLung Cancer Diagnosis and TreatmentCancer, Hypoxia, and Metabolism

LKB1 Expression Correlates with Increased Survival in Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy and Bevacizumab

Bonanno, Laura, De Paoli, Angela, Zulato, Elisabetta, Esposito, Giovanni, Calabrese, Fiorella, Favaretto, Adolfo, Santo, Antonio, Conte, Alessandro Del +12 more·2017·Clinical Cancer Research

DOI 10.1158/1078-0432.ccr-16-2410

Published version of a preprint

Open this paper in CoChat — free account

Abstract

Purpose: LKB1 is a key sensor of metabolic stress, including hypoxia and glucose deprivation, two features of the tumor microenvironment exacerbated by antiangiogenic therapy. We investigated the role of LKB1 as a potential predictive marker of sensitivity to bevacizumab in advanced non–small cell lung cancer (aNSCLC). Experimental design: We retrospectively analyzed LKB1 expression by IHC in 98 samples from 125 patients with aNSCLC, including 59 patients treated with chemotherapy and 39 treated with chemotherapy plus bevacizumab. IHC intensity was recoded in two classes (negative/weak vs. moderate/intense) and correlated with outcome according to treatment arm. Patient-derived tumor xenografts (PDXs) were used to investigate mechanisms involved in preclinical models. Results: In the whole study population (125), median OS and PFS were 11.7 [95% confidence interval (CI), 9.1–15.3] and 6.7 (95% CI, 5.7–7.2) months, respectively. Differential impact of the marker on outcome of the 98 patients was highlighted according to the treatment. Patients with negative/weak LKB1 status did not have a statistically significant benefit from bevacizumab added to chemotherapy (HR for patients treated with bevacizumab: 0.89; 95% CI, 0.51–1.56; P = 0.6803), whereas patients expressing moderate/intense LKB1 and receiving bevacizumab had significant lower risk of death compared with those not receiving bevacizumab (HR, 0.26; 95% CI, 0.10–0.64; P = 0.0035). Loss of LKB1 was associated with reduced AMPK activation in PDXs and increased tumor necrosis following bevacizumab administration, highlighting impaired control of the metabolic stress caused by this antiangiogenic drug. Conclusions: Our data hint at a possible predictive impact of LKB1 expression in patients with aNSCLC treated with chemotherapy plus bevacizumab. Clin Cancer Res; 23(13); 3316–24. ©2017 AACR.

Integrity signals

Registry

Crossref · 10.1158/1078-0432.ccr-16-2410

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

NSCLC cells with KRAS and KEAP1 co-alterations rely on GLUT8 uptake to route glucose into serine biosynthesis.
“KRAS and KEAP1 co-altered NSCLC cells display chemically tractable selective dependence on GLUT8-mediated uptake for effective diversion of glucose towards the serine biosynthetic pathway165”
From Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy (2019) · cites this paper as [165]

Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer
Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D. R., Steins, M., Ready, N. E., Chow, L. Q., Vokes, E. E., Felip, E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1507643 · Cited by 9,335 · see citing works
mTOR Signaling in Growth Control and Disease
Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509 · see citing works
Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer
Brahmer, J., Reckamp, K. L., Baas, P., Crinò, L., Eberhardt, W. E. E., Poddubskaya, E., Antonia, S., Pluzanski, A., Vokes, E. E., Holgado, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504627 · Cited by 8,447 · see citing works
Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial
Herbst, R. S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J. L., Han, J.-Y., Molina, J., Kim, J.-H., Arvis, C. D., Ahn, M.-J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01281-7 · Cited by 6,449 · see citing works
AMPK: a nutrient and energy sensor that maintains energy homeostasis
Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3311 · Cited by 4,602 · see citing works
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089 · see citing works
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial
Fehrenbacher, L., Spira, A., Ballinger, M., Kowanetz, M., Vansteenkiste, J., Mazieres, J., Park, K., Smith, D., Artal-Cortes, A., Lewanski, C., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00587-0 · Cited by 2,756 · see citing works
Somatic mutations affect key pathways in lung adenocarcinoma
Ding, L., Getz, G., Wheeler, D. A., Mardis, E. R., McLellan, M. D., Cibulskis, K., Sougnez, C., Greulich, H., Muzny, D. M., Morgan, M. B., et al. (2008) · Nature · doi:10.1038/nature07423 · Cited by 2,681 · see citing works
The LKB1-AMPK pathway: metabolism and growth control in tumour suppression
Shackelford, D. B., & Shaw, R. J. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2676 · Cited by 1,943 · see citing works
The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress
Shaw, R. J., Kosmatka, M., Bardeesy, N., Hurley, R. L., Witters, L. A., DePinho, R. A., & Cantley, L. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308061100 · Cited by 1,797 · see citing works
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial
Garon, E. B., Ciuleanu, T.-E., Arrieta, O., Prabhash, K., Syrigos, K. N., Goksel, T., Park, K., Gorbunova, V., Kowalyszyn, R. D., Pikiel, J., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60845-x · Cited by 1,309 · see citing works
LKB1 modulates lung cancer differentiation and metastasis
Ji, H., Ramsey, M. R., Hayes, D. N., Fan, C., McNamara, K., Kozlowski, P., Torrice, C., Wu, M. C., Shimamura, T., Perera, S. A., et al. (2007) · Nature · doi:10.1038/nature06030 · Cited by 1,064 · see citing works
Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial
Reck, M., Kaiser, R., Mellemgaard, A., Douillard, J.-Y., Orlov, S., Krzakowski, M., von Pawel, J., Gottfried, M., Bondarenko, I., Liao, M., et al. (2014) · The Lancet Oncology · doi:10.1016/s1470-2045(13)70586-2 · Cited by 951 · see citing works
Co-occurring Genomic Alterations Define Major Subsets of KRAS -Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities
Skoulidis, F., Byers, L. A., Diao, L., Papadimitrakopoulou, V. A., Tong, P., Izzo, J., Behrens, C., Kadara, H., Parra, E. R., Canales, J. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1236 · Cited by 936 · see citing works
The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis
Liang, J., Shao, S. H., Xu, Z.-X., Hennessy, B. T., Ding, Z., Larrea, M. D., Kondo, S., Dumont, D. J., Gutterman, J. U., Walker, C. L., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1537 · Cited by 868 · see citing works
Management of non-small-cell lung cancer: recent developments
Reck, M., Heigener, D. F., Mok, T. S. K., Soria, J., & Rabe, K. F. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61502-0 · Cited by 714 · see citing works
Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung.
Sánchez‐Céspedes, M., Parrella, P., Esteller, M., Nomoto, S., Trink, B., Engles, J. M., Westra, W. H., Herman, J. G., & Sidransky, D. (2002) · PubMed · Cited by 626 · see citing works
LKB1 and AMPK and the cancer-metabolism link - ten years after
Hardie, D. G., & Alessi, D. R. (2013) · BMC Biology · doi:10.1186/1741-7007-11-36 · Cited by 298 · see citing works
Biomarkers to predict the clinical efficacy of bevacizumab in cancer
Jubb, A. M., & Harris, A. L. (2010) · The Lancet Oncology · doi:10.1016/s1470-2045(10)70232-1 · Cited by 293 · see citing works
AMP-activated protein kinase (AMPK) beyond metabolism: A novel genomic stress sensor participating in the DNA damage response pathway
Sanli, T., Steinberg, G. R., Singh, G., & Tsakiridis, T. (2014) · Cancer Biology & Therapy · doi:10.4161/cbt.26726 · Cited by 220 · see citing works
Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells
Sanli, T., Rashid, A., Liu, C., Harding, S. M., Bristow, R. G., Cutz, J.-C., Singh, G., Wright, J. R., & Tsakiridis, T. K. (2010) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2010.03.005 · Cited by 216 · see citing works
Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer
Molina‐Vila, M. Á., Bertrán-Alamillo, J., Gascó, A., Mayo‐de‐las‐Casas, C., Sanchez-Ronco, M., Pujantell-Pastor, L., Bonanno, L., Favaretto, A. G., Cardona, A. F., Vergnenégre, A., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-2391 · Cited by 181 · see citing works
Self-citation
Epigenetic inactivation of LKB1 in primary tumors associated with the Peutz-Jeghers syndrome
Esteller, M., Avizienyte, E., Corn, P. G., Lothe, R. A., Baylin, S. B., Aaltonen, L. A., & Herman, J. G. (2000) · Oncogene · doi:10.1038/sj.onc.1203227 · Cited by 179 · see citing works
Prognostic and Predictive Value inKRASin Non–Small-Cell Lung Cancer: A Review
Wood, K., Hensing, T., Malik, R., & Salgia, R. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2016.0405 · Cited by 164 · see citing works
Frequent homozygous deletion of the LKB1/STK11 gene in non-small cell lung cancer
Gill, R. K., Yang, S.-H., Meerzaman, D. M., Mechanic, L. E., Bowman, E. D., Jeon, H.-S., Roy‐Chowdhuri, S., Shakoori, A., Dracheva, T., Hong, K.-M., et al. (2011) · Oncogene · doi:10.1038/onc.2011.98 · Cited by 123 · see citing works
Immunohistochemical Loss of LKB1 Is a Biomarker for More Aggressive Biology in KRAS -Mutant Lung Adenocarcinoma
Calles, A., Sholl, L. M., Rodig, S. J., Pelton, A. K., Hornick, J. L., Butaney, M., Lydon, C., Dahlberg, S. E., Oxnard, G. R., Jackman, D. M., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-3112 · Cited by 115 · see citing works
Novel and natural knockout lung cancer cell lines for the LKB1/STK11 tumor suppressor gene
Carretero, J., Medina, P. P., Pı́o, R., Montuenga, L. M., & Sánchez‐Céspedes, M. (2004) · Oncogene · doi:10.1038/sj.onc.1207502 · Cited by 114 · see citing works
Patient-Derived Xenografts of Non Small Cell Lung Cancer: Resurgence of an Old Model for Investigation of Modern Concepts of Tailored Therapy and Cancer Stem Cells
Moro, M., Bertolini, G., Tortoreto, M., Pastorino, U., Sozzi, G., & Roz, L. (2012) · BioMed Research International · doi:10.1155/2012/568567 · Cited by 98 · see citing works
Self-citation
Different prognostic impact ofSTK11mutations in non-squamous non-small-cell lung cancer
Pécuchet, N., Laurent‐Puig, P., Mansuet‐Lupo, A., Legras, A., Alifano, M., Pallier, K., Didelot, A., Gibault, L., Danel, C. J., Just, P., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.6379 · Cited by 87 · see citing works
Glycolytic Phenotype and AMP Kinase Modify the Pathologic Response of Tumor Xenografts to VEGF Neutralization
Nardo, G., Favaro, E., Curtarello, M., Moserle, L., Zulato, E., Persano, L., Rossi, E. M. C., Esposito, G., Crescenzi, M., Casanovas, O., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-11-0242 · Cited by 72 · see citing works
Self-citation
VEGF-Targeted Therapy Stably Modulates the Glycolytic Phenotype of Tumor Cells
Curtarello, M., Zulato, E., Nardo, G., Valtorta, S., Guzzo, G., Rossi, E. M. C., Esposito, G., Msaki, A., Pastò, A., Rasola, A., et al. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2037 · Cited by 71 · see citing works
Self-citation
AMPK regulates metabolism and survival in response to ionizing radiation
Zannella, V. E., Cojocari, D., Hilgendorf, S., Vellanki, R. N., Chung, S., Wouters, B. G., & Koritzinsky, M. (2011) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2011.05.049 · Cited by 68 · see citing works
Platinum drugs and DNA repair mechanisms in lung cancer.
Bonanno, L., Favaretto, A. G., & Rosell, R. (2014) · PubMed · Cited by 65 · see citing works
Self-citation
Specific pattern of LKB1 and phospho-acetyl-CoA carboxylase protein immunostaining in human normal tissues and lung carcinomas
Conde, E., Suárez‐Gauthier, A., García-García, E., López‐Ríos, F., Encuentra, Á. L., García‐Luján, R., Morente, M. M., Sánchez-Verde, L., & Sánchez‐Céspedes, M. (2007) · Human Pathology · doi:10.1016/j.humpath.2007.01.022 · Cited by 59 · see citing works
Prognostic and predictive implications of EGFR mutations, EGFR copy number and KRAS mutations in advanced stage lung adenocarcinoma.
Bonanno, L., Schiavon, M., Nardo, G., Bertorelle, R., Bonaldi, L., Galligioni, A., Indraccolo, S., Pasello, G., Rea, F., & Favaretto, A. G. (2010) · PubMed · Cited by 50 · see citing works
Self-citation
Prognostic significance of AMPK activation in advanced stage colorectal cancer treated with chemotherapy plus bevacizumab
Zulato, E., Bergamo, F., Paoli, A. D., Griguolo, G., Esposito, G., Salvo, G. L. D., Mescoli, C., Rugge, M., Nardin, M., Grazia, L., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.274 · Cited by 48 · see citing works
Self-citation
LKB1-AMPK axis revisited
Kottakis, F., & Bardeesy, N. M. (2012) · Cell Research · doi:10.1038/cr.2012.108 · Cited by 38 · see citing works
Role of Genotyping in Non-Small Cell Lung Cancer Treatment
Bonanno, L., Favaretto, A. G., Rugge, M., Tarón, M., & Rosell, R. (2011) · Drugs · doi:10.2165/11597700-000000000-00000 · Cited by 28 · see citing works
Self-citation
Weekly paclitaxel plus bevacizumab versus docetaxel as second or third-line treatment in advanced non-squamous non-small cell lung cancer (NSCLC): Results from the phase III study IFCT-1103 ULTIMATE.
Cortot, A. B., Audigier-Valette, C., Molinier, O., Moulec, S. L., Barlési, F., Zalcman, G., Dumont, P., Pouessel, D., Poulet, C., Souquet, P. J., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.9005 · Cited by 24 · see citing works
Metabolic effects of anti-angiogenic therapy in tumors
Zulato, E., Curtarello, M., Nardo, G., & Indraccolo, S. (2012) · Biochimie · doi:10.1016/j.biochi.2012.01.001 · Cited by 17 · see citing works
Self-citation
LKB1 regulates development and the stress response in Dictyostelium
Veeranki, S., Hwang, S., Sun, T., Kim, B., & Kim, L. (2011) · Developmental Biology · doi:10.1016/j.ydbio.2011.10.006 · Cited by 15 · see citing works
International Experts Panel Meeting of the Italian Association of Thoracic Oncology on Antiangiogenetic Drugs for Non–Small Cell Lung Cancer: Realities and Hopes
de Marinis, F., Bria, E., Ciardiello, F., Crinò, L., Douillard, J.-Y., Griesinger, F., Lambrechts, D., Pérol, M., Ramalingam, S. S., Smit, E. F., et al. (2016) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2016.03.015 · Cited by 9 · see citing works

Flagged first, then by citations

2 of the 44 references couldn’t be matched to a known paper.

Sorted by citations

STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma
Skoulidis, F., Goldberg, M. E., Greenawalt, D. M., Hellmann, M. D., Awad, M. M., Gainor, J. F., Schrock, A. B., Hartmaier, R. J., Trabucco, S. E., Gay, L., et al. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0099 · Cited by 1,641 · see citing works
Exploring treatment options in cancer: tumor treatment strategies
Liu, B., Zhou, H., Tan, L., Siu, K. T. H., & Guan, X.-Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01856-7 · Cited by 1,201 · see citing works
Lung cancer immunotherapy: progress, pitfalls, and promises
Lahiri, A., Maji, A., Potdar, P. D., Singh, N., Parikh, P., Bisht, B., Mukherjee, A., & Paul, M. K. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01740-y · Cited by 1,102 · see citing works
Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy
Skoulidis, F., & Heymach, J. V. (2019) · Nature Reviews Cancer · doi:10.1038/s41568-019-0179-8 · Cited by 1,019 · see citing works
Molecular Mechanisms and Future Implications of VEGF/VEGFR in Cancer Therapy
Patel, S. A., Nilsson, M. B., Le, X., Cascone, T., Jain, R. K., & Heymach, J. V. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-22-1366 · Cited by 508 · see citing works
Oncogenic pathways and the electron transport chain: a dangeROS liaison
Raimondi, V., Ciccarese, F., & Ciminale, V. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0651-y · Cited by 225 · see citing works
Self-citation
LKB1/AMPK Pathway and Drug Response in Cancer: A Therapeutic Perspective
Ciccarese, F., Zulato, E., & Indraccolo, S. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/8730816 · Cited by 147 · see citing works
Self-citation
Systematic Review of Patient-Derived Xenograft Models for Preclinical Studies of Anti-Cancer Drugs in Solid Tumors
Koga, Y., & Ochiai, A. (2019) · Cells · doi:10.3390/cells8050418 · Cited by 107 · see citing works
Metformin Enhances Cisplatin-Induced Apoptosis and Prevents Resistance to Cisplatin in Co-mutated KRAS/LKB1 NSCLC
Moro, M., Caiola, E., Ganzinelli, M., Zulato, E., Rulli, E., Marabese, M., Centonze, G., Busico, A., Pastorino, U., de Braud, F., et al. (2018) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2018.07.102 · Cited by 106 · see citing works
Self-citation
Immunotherapy in small-cell lung cancer: from molecular promises to clinical challenges
Pavan, A., Attili, I., Pasello, G., Guarneri, V., Conte, P., & Bonanno, L. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0690-1 · Cited by 96 · see citing works
Self-citation
Quicker, deeper and stronger imaging: A review of tumor-targeted, near-infrared fluorescent dyes for fluorescence guided surgery in the preclinical and clinical stages
Jiao, J., Zhang, J., Yang, F., Song, W., Han, D., Wen, W., & Qin, W. (2020) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2020.05.002 · Cited by 66 · see citing works
SMARCA4 mutations in KRAS ‐mutant lung adenocarcinoma: a multi‐cohort analysis
Liu, L., Ahmed, T., Petty, W. J., Grant, S. C., Ruiz, J., Lycan, T. W., Topaloĝlu, Ü., Chou, P., Miller, L. D., Hawkins, G. A., et al. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12831 · Cited by 58 · see citing works
Patient-derived xenografts as compatible models for precision oncology
Cho, S. (2020) · Laboratory Animal Research · doi:10.1186/s42826-020-00045-1 · Cited by 58 · see citing works
LKB1 and Tumor Metabolism: The Interplay of Immune and Angiogenic Microenvironment in Lung Cancer
Bonanno, L., Zulato, E., Pavan, A., Attili, I., Pasello, G., Conte, P., & Indraccolo, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081874 · Cited by 52 · see citing works
Self-citation
Prospect of immunotherapy combined with anti-angiogenic agents in patients with advanced non-small cell lung cancer
Liang, H., & Wang, M. (2019) · Cancer Management and Research · doi:10.2147/cmar.s212238 · Cited by 53 · see citing works
LKB1 Deficiency Renders NSCLC Cells Sensitive to ERK Inhibitors
Caiola, E., Iezzi, A., Tomanelli, M., Bonaldi, E., Scagliotti, A., Colombo, M., Guffanti, F., Micotti, E., Garassino, M. C., Minoli, L., et al. (2019) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2019.10.009 · Cited by 45 · see citing works
Role of next generation sequencing-based liquid biopsy in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors: impact of STK11, KRAS and TP53 mutations and co-mutations on outcome
Pavan, A., Bragadin, A. B., Calvetti, L., Ferro, A., Zulato, E., Attili, I., Nardo, G., Maso, A. D., Frega, S., Menin, A. G., et al. (2021) · Translational Lung Cancer Research · doi:10.21037/tlcr-20-674 · Cited by 47 · see citing works
Self-citation
Establishment of patient derived xenografts as functional testing of lung cancer aggressiveness
Moro, M., Bertolini, G., Caserini, R., Borzi, C., Boeri, M., Fabbri, A., Leone, G., Gasparini, P., Galeone, C., Pelosi, G., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-06912-7 · Cited by 44 · see citing works
Self-citation
Combination immunotherapy strategies in advanced non-small cell lung cancer (NSCLC): Does biological rationale meet clinical needs?
Attili, I., Passaro, A., Pavan, A., Conte, P., de Marinis, F., & Bonanno, L. (2017) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2017.09.007 · Cited by 44 · see citing works
Self-citation
LKB1 loss is associated with glutathione deficiency under oxidative stress and sensitivity of cancer cells to cytotoxic drugs and γ-irradiation
Zulato, E., Ciccarese, F., Agnusdei, V., Pinazza, M., Nardo, G., Iorio, E., Curtarello, M., Silic‐Benussi, M., Rossi, E. M. C., Venturoli, C., et al. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.019 · Cited by 42 · see citing works
Self-citation
Inactivation of AMPK leads to attenuation of antigen presentation and immune evasion in lung adenocarcinoma
Gao, Y., Päivinen, P., Tripathi, S., Domènech-Moreno, E., Wong, I. P. L., Vaahtomeri, K., Nagaraj, A. S., Talwelkar, S. S., Foretz, M., Verschuren, E. W., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2049 · Cited by 40 · see citing works
Phosphorylated Acetyl-CoA Carboxylase Is Associated with Clinical Benefit with Regorafenib in Relapsed Glioblastoma: REGOMA Trial Biomarker Analysis
Indraccolo, S., Salvo, G. L. D., Verza, M., Caccese, M., Esposito, G., Piga, I., Bianco, P. D., Pizzi, M., Gardiman, M. P., Eoli, M., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-4055 · Cited by 36 · see citing works
Self-citation
CAB39 promotes cisplatin resistance in bladder cancer via the LKB1-AMPK-LC3 pathway
Gao, D., Wang, R.-C., Gong, Y., Yu, X., Niu, Q., Yang, E., Fan, G., Ma, J., Chen, C., Tao, Y., et al. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.09.017 · Cited by 24 · see citing works
Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy
Mazzaschi, G., Leonetti, A., Minari, R., Gnetti, L., Quaini, F., Tiseo, M., & Facchinetti, F. (2021) · Current Treatment Options in Oncology · doi:10.1007/s11864-021-00891-8 · Cited by 20 · see citing works
Outcomes following KRASG12C inhibitor treatment in patients with KRASG12C-mutated solid tumors: A systematic review and meta-analysis
Chen, Q., Lin, W., Zhou, X.-X., Cao, Z., Feng, X., Gao, Y., & He, J. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107060 · Cited by 21 · see citing works
Impact of KRAS Mutation Subtypes and Co-Occurring Mutations on Response and Outcome in Advanced NSCLC Patients following First-Line Treatment
Sun, Y., Li, Z., Jian, H., Xia, L., & Lü, S. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11144003 · Cited by 17 · see citing works
The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade
Cui, Y., Sun, Y., Li, D., Zhang, Y., Zhang, Y., Cao, D., & Cao, X. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1275543 · Cited by 14 · see citing works
Atezolizumab prolongs overall survival over docetaxel in advanced non-small-cell lung cancer patients harboring STK11 or KEAP1 mutation
Nie, W., Gan, L., Wang, X., Gu, K., Qian, F.-F., Hu, M.-J., Zhang, D., Chen, S.-Q., Lü, J., Cao, S.-H., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2020.1865670 · Cited by 13 · see citing works
LKB1 expression and the prognosis of lung cancer
Lin, C., Lin, X., Lin, K., Tan, J., Wei, C., & Liu, T. (2021) · Medicine · doi:10.1097/md.0000000000027841 · Cited by 13 · see citing works
Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis
Hu, D., Zhou, Y., Ma, H., Tao, M.-M., Huang, Q., Yang, Z., & Zhou, Q. (2023) · BMC Pulmonary Medicine · doi:10.1186/s12890-023-02472-x · Cited by 12 · see citing works
Cloning and prokaryotic expression of the chicken liver kinase B1 (LKB1) and its localization in liver, heart and hypothalamus
Zhang, K., Shi, Y., Xu, P., Huang, C., Zhou, C., Liu, P., Hu, R., Yu, Z., Li, G., Hu, G., et al. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.12.195 · Cited by 12 · see citing works
Expression profiling of ubiquitin-related genes in LKB1 mutant lung adenocarcinoma
Wang, G., Bie, F., Qu, X. H., Yang, X., Liu, S., Wang, Y., Huang, C., Wang, K., & Du, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-31592-2 · Cited by 9 · see citing works
Influence and mechanism of lung cavitation development on antiangiogenic therapy: is cavitation the new caveat?
Calvetti, L., & Aprile, G. (2019) · Translational Lung Cancer Research · doi:10.21037/tlcr.2019.08.19 · Cited by 9 · see citing works
Insights into targeting LKB1 in tumorigenesis
Trelford, C. B., & Shepherd, T. G. (2024) · Genes & Diseases · doi:10.1016/j.gendis.2024.101402 · Cited by 9 · see citing works
LKB1 mutations are not associated with the efficacy of first-line and second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC): a post hoc analysis of the TAILOR trial
Vernieri, C., Ganzinelli, M., Rulli, E., Farina, G., Bettini, A., Bareggi, C., Rosso, L., Signorelli, D., Galli, G., Russo, G. L., et al. (2020) · ESMO Open · doi:10.1136/esmoopen-2020-000748 · Cited by 8 · see citing works
Self-citation
Genetic variants in LKB1 / AMPK / mTOR pathway are associated with clinical outcomes of chemotherapy in non‐small cell lung cancer
Choi, S. H., Do, S. K., Lee, S. Y., Choi, J. E., Kang, H., Hong, M. J., Lee, J. H., Lee, W. K., Jeong, J. Y., Shin, K. M., et al. (2022) · Thoracic Cancer · doi:10.1111/1759-7714.14688 · Cited by 8 · see citing works
AMPK variant, a candidate of novel predictor for chemotherapy in metastatic colorectal cancer: A meta‐analysis using TRIBE, MAVERICC and FIRE3
Tokunaga, R., Cao, S., Naseem, M., Battaglin, F., Lo, J. H., Arai, H., Loupakis, F., Stintzing, S., Puccini, A., Berger, M. D., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32261 · Cited by 6 · see citing works
Tumor vascular disruption and cGAS–STING activation by gambogic amide-loaded nanomicelles for multiple synergistic treatment of triple-negative breast cancer
Gui, Z., Zhao, L., Liu, S., & Zhang, L. (2025) · Cancer Nanotechnology · doi:10.1186/s12645-025-00341-2 · Cited by 4 · see citing works
Hotspots and trends in liver kinase B1 research: A bibliometric analysis
Song, Y., Zhao, F., Ma, W., & Li, G. (2021) · PLoS ONE · doi:10.1371/journal.pone.0259240 · Cited by 4 · see citing works
LKB1 Loss Assessed by Immunohistochemistry as a Prognostic Marker to First-Line Therapy in Advanced Non-Small-Cell Lung Cancer
Avilés‐Salas, A., Díaz-García, D. A., Lara‐Mejía, L., Cardona, A. F., Orozco‐Morales, M., Catalán, R., Hernández‐Pedro, N., Rios-Garcia, E., Ramos-Ramírez, M., & Arrieta, O. G. (2022) · Current Oncology · doi:10.3390/curroncol30010027 · Cited by 4 · see citing works
Clinical Benefit from Docetaxel +/− Ramucirumab Is Not Associated with Mutation Status in Metastatic Non-Small-Cell Lung Cancer Patients Who Progressed on Platinum Doublets and Immunotherapy
Qin, K., Wang, K., Li, S., Hong, L., Padmakumar, P., Rinsurongkawong, W., Hubert, S. M., Le, X., Vokes, N. I., Rai, K., et al. (2024) · Cancers · doi:10.3390/cancers16050935 · Cited by 3 · see citing works
Pan-Cancer Computational Analysis of RKIP (PEBP1) and LKB1 (STK11) Co-Expression Highlights Distinct Immunometabolic Dynamics and Therapeutic Responses Within the Tumor Microenvironment
Skouradaki, E., Zaravinos, A., Παναγοπούλου, Μ., Chatzaki, Ε., Dovrolis, N., & Baritaki, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26157145 · Cited by 3 · see citing works
Systematic literature review of real-world evidence on overall survival in cancer patients before and after the approval of anti-PD-(L)1 therapy
Nayak, D., Akers, K. G., Frederickson, A. M., Mbous, Y. P. V., & Aguiar‐Ibáñez, R. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1615795 · Cited by 2 · see citing works
Tumor cavitation in patients with non-small-cell lung cancer receiving anti-angiogenic therapy with apatinib
Cai, Q., Hu, K. R., Dong, S., Li, X., Hu, S., Deng, W., & Ou, W. (2024) · Translational Lung Cancer Research · doi:10.21037/tlcr-24-465 · Cited by 2 · see citing works
Preclinical In Vivo Animal Xenograft Models: Heterogeneity and Biomarkers of Therapeutic Response and Resistance
Zaky, M. Y., Lamloum, N. S., Ahmed, N. A., & Ahmed, O. M. (2025) · Springer eBooks · doi:10.1007/978-981-97-5742-8_5 · Cited by 2 · see citing works
Tumor Angiogenesis
Heymach, J. V., Zurita‐Saavedra, A., Kopetz, S., Cascone, T., Nilsson, M. B., & Guijarro, I. (2022) · Holland‐Frei Cancer Medicine · doi:10.1002/9781119000822.hfcm017.pub2 · Cited by 2 · see citing works
Editorial on “The AvaALL Randomized Clinical Trial”
Bonanno, L., Pavan, A., Pasello, G., & Indraccolo, S. (2019) · Journal of Thoracic Disease · doi:10.21037/jtd.2019.02.62 · Cited by 1 · see citing works
Self-citation
Metformin Plus Tyrosine Kinase Inhibitors in Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer—Reply
Arrieta, O. G., Ramírez-Tirado, L. A., & Zatarain-Barrón, Z. L. (2020) · JAMA Oncology · doi:10.1001/jamaoncol.2020.0062 · Cited by 1 · see citing works
The Tumor and Its Microenvironment as Complementary Sources of Cancer Biomarkers
Roy, R., Man, E., Aldakhlallah, R., Rashes, E. R., & Moses, M. A. (2022) · Springer eBooks · doi:10.1007/978-3-030-98950-7_22
Data from Inactivation of AMPK Leads to Attenuation of Antigen Presentation and Immune Evasion in Lung Adenocarcinoma
Gao, Y., Päivinen, P., Tripathi, S., Domènech‐Moreno, E., Wong, I. P. L., Vaahtomeri, K., Nagaraj, A. S., Talwelkar, S. S., Foretz, M., Verschuren, E. W., et al. (2023) · doi:10.1158/1078-0432.c.6531086
Data from Inactivation of AMPK Leads to Attenuation of Antigen Presentation and Immune Evasion in Lung Adenocarcinoma
Gao, Y., Päivinen, P., Tripathi, S., Domènech‐Moreno, E., Wong, I. P. L., Vaahtomeri, K., Nagaraj, A. S., Talwelkar, S. S., Foretz, M., Verschuren, E. W., et al. (2023) · doi:10.1158/1078-0432.c.6531086.v1
Liver kinase B1 expression is associated with improved prognosis and tumor immune microenvironment features in small cell lung cancer
Maso, A. D., Ferrarini, F., Esposito, G., Minuzzo, S. A., Puggia, A. M., Pezzuto, F., Zulato, E., Bao, L. C., Nuzzo, M. D., Ferro, A., et al. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1552506
Self-citation
SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma
Costa, E. A., de Mello, B. V., Wohlhieter, C. A., Nandakumar, S., Tischfield, S., Zhan, Y. A., Sridhar, H., Kinyua, D., de Stanchina, E., Kang, W., et al. (2026) · Translational Oncology · doi:10.1016/j.tranon.2026.102915

P3.03-027 LKB1 Loss Is Associated with Resistance to Anti-Angiogenic Therapy in Non-Small Cell Lung Cancer Mouse Models
Guijarro, I., Poteete, A., Fan, Y.-H., Cho, S., Tong, P., Roarty, E. B., Nilsson, M. B., Rodriguez‐Canales, J., Mino, B., Cuentas, E. P., et al. (2017) · Journal of Thoracic Oncology · doi:10.1016/j.jtho.2017.09.1654
Abstract 3272: LKB1 loss is associated with resistance to VEGF inhibitors in non-small cell lung cancer (NSCLC)
Guijarro, I., Poteete, A., Yang, C., Roarty, E. B., Nilsson, M. B., Sun, H., Tong, P., Chang, E. Q., Rodriguez‐Canales, J., Mino, B., et al. (2016) · Cancer Research · doi:10.1158/1538-7445.am2016-3272
Predictive value of LDH kinetics in bevacizumab treatment and survival of patients with advanced NSCLC
Li, B., Li, C., Guo, M., Shang, S., Li, X., Xie, P., Sun, X., Yu, J., & Wang, L. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s171566 · Cited by 22 · see citing works
Reduced expression of liver kinase B1 and Beclin1 is associated with the poor survival of patients with non-small cell lung cancer
Jiang, L., Liang, X., Liu, M., Wang, W., Ma, J., Guo, Q., HAN, L., Yang, C., & Nan, K. (2014) · Oncology Reports · doi:10.3892/or.2014.3432 · Cited by 23 · see citing works
New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer
Niki, M., Yokoi, T., Kurata, T., & Nomura, S. (2017) · Lung Cancer Targets and Therapy · doi:10.2147/lctt.s138887 · Cited by 20 · see citing works

Authors: Bonanno, L., De Paoli, A., Zulato, E., Esposito, G., Calabrese, F., Favaretto, A., Santo, A., Conte, A. D., Chilosi, M., Oniga, F., Sozzi, G., Moro, M., Ciccarese, F., Nardo, G., Bertorelle, R., Candiotto, C., De Salvo, G. L., Amadori, A., Conte, P., & Indraccolo, S.
Affiliations: Istituto Oncologico Veneto (IT)
2Clinical Trials and Biostatistics Unit, Istituto Oncologico Veneto IOV-IRCCS, Padova, Italy.
University of Padua (IT)
Ca' Foncello Hospital (IT)
Azienda Ospedaliera Universitaria Integrata Verona (IT)
Azienda Ospedaliera Santa Maria Degli Angeli (IT)
University of Verona (IT)
Ospedale dell' Angelo (IT)
Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
Corresponding author: Indraccolo, Stefano
ORCID: Bonanno, Laura
Zulato, Elisabetta
Esposito, Giovanni
Calabrese, Fiorella
Favaretto, Adolfo
Santo, Antonio
Conte, Alessandro Del
Chilosi, Marco
Sozzi, Gabriella
Moro, Massimo
Ciccarese, Francesco
Nardo, Giorgia
Bertorelle, Roberta
Candiotto, Cinzia
Conte, PierFranco
Indraccolo, Stefano
Venue: Clinical Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2017-07-01
Volume: 23
Issue: 13
Pages: 3316-3324
ISSN: 1078-0432 (ISSN-L)
1557-3265
DOI: 10.1158/1078-0432.ccr-16-2410
OpenAlex: W2581547394
Cited by: 53
References: 44
Citations by year: 2026: 1 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 11 · 2018: 4 · 2017: 2
FWCI: 5.43
Type: journal article
Language: en
Open access: closed
Locations: Clinical Cancer Research (publishedVersion)
PubMed (publishedVersion)
Padua Research Archive (University of Padova) (submittedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords: LKB1, non-small cell lung cancer, bevacizumab, anti-angiogenic therapy, predictive biomarkers, chemotherapy, overall survival, progression-free survival, AMPK activation, tumor necrosis, tumor microenvironment, patient-derived xenografts
MeSH terms: Bevacizumab, AMP-Activated Protein Kinase Kinases, Aged, Animals, Carcinoma, Non-Small-Cell Lung, Female, Humans, Male, Middle Aged, Neovascularization, Pathologic, Gene Expression Regulation, Neoplastic, Protein Serine-Threonine Kinases, Disease-Free Survival, Angiogenesis Inhibitors, Xenograft Model Antitumor Assays, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

LKB1 Expression Correlates with Increased Survival in Patients with Advanced Non–Small Cell Lung Cancer Treated with Chemotherapy and Bevacizumab

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks