Review
Medicine, General & Internal
Baharia Mograbi, Simon Heeke, Paul Hofman
Summary: This review discusses the utilization of immunotherapy in the first-line treatment of NSCLC, focusing on the association between mutations in STK11/LKB1 and the lack of response to immunotherapy. It also highlights the potential directions and key points for future research in this area.
Article
Medicine, Research & Experimental
Puneeth Iyengar, Aakash Y. . Gandhi, Jorge Granados, Tong Guo, Arun Gupta, Jinhai Yu, Ernesto M. . Llano, Faya Zhang, Ang Gao, Asha Kandathil, Dorothy Williams, Boning Gao, Luc Girard, Venkat S. . Malladi, John M. . Shelton, Bret M. . Evers, Raquibul Hannan, Chul Ahn, John D. . Minna, Rodney E. . Infante
Summary: Cancer cachexia (CC) is a wasting syndrome observed in 50% of solid tumor patients, and its management is limited by the lack of biomarkers and knowledge of driving molecules. This study identified mutations in serine/threonine kinase 11 (STK11/LKB1) as a driver of CC in non-small cell lung cancer (NSCLC) and colorectal carcinoma. Silencing STK11/LKB1 induced cachexia phenotype in NSCLC and colorectal carcinoma models, which was accompanied by immune cell changes and increased expression of CC-associated cytokines. Mutational analysis showed high concordance between STK11/LKB1 mutations and weight loss in NSCLC patients, suggesting its potential as a genetic biomarker for CC.
Article
Biology
Xin Zhou, Jennifer W. Li, Zirong Chen, Wei Ni, Xuehui Li, Rongqiang Yang, Huangxuan Shen, Jian Liu, Francesco J. DeMayo, Jianrong Lu, Frederic J. Kaye, Lizi Wu
Summary: This study reveals the overlap in expression patterns and potential functional redundancy of CRTC1-3 in lung cancer. A dominant-negative mutant (dnCRTC) was designed and shown to efficiently inhibit aberrant oncogenic transcription induced by LKB1 deficiency, specifically blocking the growth of LKB1-inactivated lung cancer. These findings provide direct evidence for the essential role of the CRTC-CREB activation in promoting the malignant phenotypes of LKB1-null lung cancer, suggesting a novel therapeutic target.
Review
Oncology
Gloriana Ndembe, Ilenia Intini, Elisa Perin, Mirko Marabese, Elisa Caiola, Paolo Mendogni, Lorenzo Rosso, Massimo Broggini, Marika Colombo
Summary: Loss of LKB1 in non-small cell lung cancer leads to enhanced metabolic avidity, making the tumors aggressive and resistant to various therapies. Exploiting co-vulnerabilities and utilizing strategies such as inducing metabolic stress and targeting downstream proteins of LKB1 can provide effective treatment options for these patients.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Alessandro Di Federico, Andrea De Giglio, Claudia Parisi, Francesco Gelsomino
Summary: Immune checkpoint inhibitors (ICIs) are essential in treating advanced non-small cell lung cancer (NSCLC), with PD-L1 expression as the current biomarker for predicting response. STK11/LKB1 and KEAP1 mutations are associated with poor outcomes in NSCLC patients receiving ICI, especially in the presence of concurrent KRAS mutations.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Cell Biology
Abubakar Wani, Sweilem B. Al Rihani, Ankita Sharma, Brenna Weadick, Rajgopal Govindarajan, Sameer U. Khan, Parduman R. Sharma, Ashish Dogra, Utpal Nandi, Chilakala N. Reddy, Sonali S. Bharate, Gurdarshan Singh, Sandip B. Bharate, Ram A. Vishwakarma, Amal Kaddoumi, Ajay Kumar
Summary: This study found that crocetin can induce autophagy in Alzheimer's disease, helping to clear Aβ and improve memory function.
Article
Oncology
Martin F. Berthelsen, Siv L. Leknes, Maria Riedel, Mette A. Pedersen, Justin V. Joseph, Henrik Hager, Mikkel H. Vendelbo, Martin K. Thomsen
Summary: This study using a mouse model of lung cancer showed that loss of Stk11 is a key driver for adenocarcinoma progression, while loss of Pten is dispensable for adenocarcinoma development.
Review
Cell Biology
Elvire Pons-Tostivint, Alexandre Lugat, Jean-Francois Fontenau, Marc Guillaume Denis, Jaafar Bennouna
Summary: The STK11/LKB1 gene codes for an important kinase involved in energy-related cellular processes, and its inactivation can lead to the progression of lung cancer and impact the tumor immune environment. Descriptive epidemiology, co-occurring genomic alterations, and prognostic impact for lung cancer patients are discussed, as well as the effects of STK11/LKB1 alterations on the immune system and response to immune checkpoint inhibitors in pre-clinical models and lung cancer cohorts.
Article
Oncology
Lujie Yang, Qin Zhang, Yanli Xiong, Zhaoqian Dang, He Xiao, Qian Chen, Xiaoyan Dai, Lei Zhang, Jianwu Zhu, Dong Wang, Mengxia Li
Summary: This study discovered that apatinib is a direct activator of AMP-activated protein kinase (AMPK), which inhibits de novo fatty acid synthesis in LKB1-mutant NSCLC. The combination of apatinib with exogenous fatty acid restriction shows promise as a treatment method for LKB1-mutant NSCLC. These findings provide a basis for the accurate and combined application of VEGFR-TKIs, including apatinib and anlotinib, in the treatment of LKB1-mutant NSCLC.
Article
Medicine, General & Internal
Yun-Suk Choi, Seong-Woon Choi, Jin-Wook Yi
Summary: This study identified TERT promoter mutations in PTC and found that they are associated with more aggressive behavior. Patients with TERT promoter mutations were older, had larger tumors, and exhibited other adverse clinical features, resulting in a poorer prognosis compared to those with wild-type TERT gene status.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Anastasios Maniakas, Ying C. Henderson, Hu Hei, Shaohua Peng, Yunyun Chen, Yujie Jiang, Shuangxi Ji, Maria Cardenas, Yulun Chiu, Diana Bell, Michelle D. Williams, Marie-Claude Hofmann, Steve E. Scherer, David A. Wheeler, Naifa L. Busaidy, Ramona Dadu, Jennifer R. Wang, Maria E. Cabanillas, Mark Zafereo, Faye M. Johnson, Stephen Y. Lai
Summary: This study developed and characterized 6 novel ATC PDX models with 4 matching cell lines, each with distinct genetic profiles. The PDX models showed remarkable resemblance to the original patient surgical specimens and had strong concordance with the original tumor in terms of genetic characteristics. These models can serve as excellent tools for preclinical therapeutic trials.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Oncology
Michael J. Koenig, Bernice A. Agana, Jacob M. Kaufman, Michael F. Sharpnack, Walter Z. Wang, Christoph Weigel, Fabio C. P. Navarro, Joseph M. Amann, Nicole Cacciato, Rajeswara Rao Arasada, Mark B. Gerstein, Vicki H. Wysocki, Christopher Oakes, David P. Carbone
Summary: The study discovered a novel association between LKB1 loss and widespread DNA demethylation in lung adenocarcinoma, leading to global hypomethylation with implications for epigenetic therapy and immunotherapy in these cancers.
Article
Multidisciplinary Sciences
Adrian Buensuceso, Jamie Lee Fritz, Olga Collins, Yudith Ramos Valdes, Matthew J. Borrelli, Gabriel E. DiMattia, Trevor G. Shepherd
Summary: In this study, the researchers found that loss of Liver kinase B1 (LKB1) and its substrate NUAK1 in high-grade serous ovarian cancer (HGSOC) leads to hyperactive NF-kappa B signaling, which suppresses reactive oxygen species (ROS) production and supports cell survival. These findings suggest that combined inhibition of NUAK1 and NF-kappa B signaling may be a novel therapeutic strategy for advanced HGSOC.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Seung Bae Rho, Hyun Jung Byun, Boh-Ram Kim, Chang Hoon Lee
Summary: This study investigates the role of LKB1 in cervical tumor angiogenesis. The results show that LKB1 inhibits angiogenesis by suppressing the expression of angiogenesis-related factors and targeting the VEGFR-2-mediated signaling pathway. The findings provide new insights into the molecular mechanisms of LKB1 in cervical cancer.
BIOMOLECULES & THERAPEUTICS
(2023)
Article
Oncology
Xiaoling Shang, Zhenxiang Li, Jian Sun, Chenglong Zhao, Jiamao Lin, Haiyong Wang
Summary: Non-squamous non-small cell lung cancer patients with STK11/KEAP1 mutations may not benefit more from both atezolizumab and docetaxel compared to wild type. However, patients with KEAP1 mutations alone and without STK11 mutations may have a better response to atezolizumab than docetaxel.
Article
Pathology
Shuanzeng Wei, Zhanyong Bing, Yuan Yao, Stephen R. Master, Prabodh Gupta
Article
Oncology
Shuanzeng Wei, David Lieberman, Jennifer J. D. Morrissette, Zubair W. Baloch, David B. Roth, Cindy McGrath
CANCER CYTOPATHOLOGY
(2016)
Article
Endocrinology & Metabolism
Shuanzeng Wei, Virginia A. LiVolsi, Zubair W. Baloch
ENDOCRINE PATHOLOGY
(2015)
Article
Endocrinology & Metabolism
Shuanzeng Wei, Virginia A. LiVolsi, Kathleen T. Montone, Jennifer J. D. Morrissette, Zubair W. Baloch
ENDOCRINE PATHOLOGY
(2015)
Article
Endocrinology & Metabolism
Shuanzeng Wei, Zubair W. Baloch, Virginia A. LiVolsi
ENDOCRINE PATHOLOGY
(2015)
Article
Endocrinology & Metabolism
Shuanzeng Wei, Virginia A. LiVolsi, Kathleen T. Montone, Jennifer J. D. Morrissette, Zubair W. Baloch
ENDOCRINE PATHOLOGY
(2016)
Article
Pathology
Shuanzeng Wei, Alain Dumas, Paul L. Zhang, Kumarasen Cooper
PATHOLOGY RESEARCH AND PRACTICE
(2016)
Article
Pathology
Shuanzeng Wei, Hormoz Ehya
Letter
Surgery
Adriana Handra-Luca, Shuanzeng Wei
Article
Cell Biology
Joyce V. Lee, Alessandro Carrer, Supriya Shah, Nathaniel W. Snyder, Shuanzeng Wei, Sriram Venneti, Andrew J. Worth, Zuo-Fei Yuan, Hee-Woong Lim, Shichong Liu, Ellen Jackson, Nicole M. Aiello, Naomi B. Haas, Timothy R. Rebbeck, Alexander Judkins, Kyoung-Jae Won, Lewis A. Chodosh, Benjamin A. Garcia, Ben Z. Stanger, Michael D. Feldman, Ian A. Blair, Kathryn E. Wellen
Article
Endocrinology & Metabolism
Shuanzeng Wei, Zubair W. Baloch, Virginia A. LiVolsi
ENDOCRINE PATHOLOGY
(2015)
Editorial Material
Endocrinology & Metabolism
Shuanzeng Wei, Virginia A. LiVolsi, Zubair W. Baloch
ENDOCRINE PATHOLOGY
(2015)
Article
Endocrinology & Metabolism
Shuanzeng Wei, Zubair W. Baloch, Virginia A. LiVolsi
ENDOCRINE PATHOLOGY
(2015)
Review
Medical Laboratory Technology
Shuanzeng Wei, Lester J. Layfield, Virginia A. LiVolsi, Kathleen T. Montone, Zubair W. Baloch
DIAGNOSTIC CYTOPATHOLOGY
(2017)