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JOURNAL ARTICLE
Shixun Han, Haonan Fan, Guoxuan Zhong, Lei Ni, Wenhao Shi, Yushan Fang, Chenliang Wang, Li Wang, Lang Song, Jianhui Zhao, Mei Tang, Bing Yang, Li Li, Xueli Bai, Qi Zhang, Tingbo Liang, Yanhui Xu, Xin-Hua Feng, Chen Ding, Dong Fang, Bin Zhao
BACKGROUND AND AIMS: Epigenetic reprogramming and escape from terminal differentiation are poorly understood enabling characteristics of liver cancer. Keratin 19 (KRT19), classically known to form the intermediate filament cytoskeleton, is a marker of stemness and worse prognosis in liver cancer. This study aimed to address the functional roles of KRT19 in liver tumorigenesis and to elucidate the underlying mechanisms. APPROACH AND RESULTS: Using multiplexed genome editing of hepatocytes in vivo, we demonstrated that KRT19 promoted liver tumorigenesis in mice...
April 1, 2024: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
#22
JOURNAL ARTICLE
Aole Zheng, Dongsheng Yang, Chunyang Pan, Qingfeng He, Xiao Zhu, Xiaoqiang Xiang, Peiying Ji
BACKGROUND: Lenvatinib's efficacy as a frontline targeted therapy for radioactive iodine-refractory thyroid carcinoma and advanced hepatocellular carcinoma owes to its inhibition of multiple tyrosine kinases. However, as a CYP3A4 substrate, lenvatinib bears susceptibility to pharmacokinetic modulation by co-administered agents. Schisantherin A (STA) and schisandrin A (SIA) - bioactive lignans abundant in the traditional Chinese medicinal Wuzhi Capsule - act as CYP3A4 inhibitors, engendering the potential for drug-drug interactions (DDIs) with lenvatinib...
March 29, 2024: European Journal of Pharmaceutical Sciences
#23
JOURNAL ARTICLE
Andrea Di Marco, Grazia Artioli, Adolfo Favaretto, Nicolò Cavasin, Umberto Basso
RATIONALE: Treatment with a combination of immune checkpoint inhibitors (ICIs) (pembrolizumab or nivolumab) and oral Tyrosine Kinase Inhibitors (TKI) targeting angiogenesis (axitinib, cabozantinib or lenvatinib) has shown benefits in terms of efficacy and survival in metastatic renal cell carcinoma (mRCC), with a favorable toxicity profile. However, some rare and serious treatment-related adverse events can be difficult to manage. PATIENT CONCERNS: Here we report the first case of an mRCC patient who, after only 2 administrations of pembrolizumab-axitinib, experienced severe multiorgan failure (MOF) with heart failure, oliguria and acute hepatitis requiring aggressive supportive treatment in intensive care unit...
March 29, 2024: Medicine (Baltimore)
#24
Ijeoma Orabueze, Inemesit Akpan, Ryan Denley
We highlight the risk of lenvatinib drug toxicity when high-risk anatomic regions are affected by angiosarcoma.
April 2024: Clinical Case Reports
#25
JOURNAL ARTICLE
Renguo Guan, Nan Zhang, Min Deng, Ye Lin, Guanjie Huang, Yizhen Fu, Zehao Zheng, Wei Wei, Chong Zhong, Haitao Zhao, Jie Mei, Rongping Guo
BACKGROUND: Lenvatinib plus Programmed Death-1 (PD-1) inhibitors (LEN-P) have been recommended in China for patients with advanced hepatocellular carcinoma (HCC). However, they provide limited survival benefits to patients with extrahepatic metastases. We aimed to investigate whether combining hepatic arterial infusion chemotherapy (HAIC) with LEN-P could improve its efficacy. MATERIALS AND METHODS: This multi-center cohort study included patients with HCC extrahepatic metastases who received HAIC combined with LEN-P (HAIC-LEN-P group, n=127) or LEN-P alone (n=103) as the primary systemic treatment between January 2019 and December 2022...
March 28, 2024: International Journal of Surgery
#26
JOURNAL ARTICLE
Jing Zhao, Dongming Yan, Yue Li, Xiaoqing Xu, Fengling Li, Shuang Zhang, Jingyi Jin, Furong Qiu
Interindividual exposure differences have been identified in oral targeted antineoplastic drugs (OADs) owing to the pharmacogenetic background of the patients and their susceptibility to multiple factors, resulting in insufficient efficacy or adverse effects. Therapeutic drug monitoring (TDM) can prevent sub-optimal concentrations of OADs and improve their clinical treatment. This study aimed to develop and validate an LC-MS/MS method for the simultaneous quantification of 11 OADs (gefitinib, imatinib, lenvatinib, regorafenib, everolimus, osimertinib, sunitinib, tamoxifen, lapatinib, fruquintinib and sorafenib) and 2 active metabolites (N-desethyl sunitinib and Z-endoxifen) in human plasma...
March 26, 2024: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
#27
JOURNAL ARTICLE
Yi Zong, Zhigang Tao, Siyi Jiang, Minyuan Wang, Weihua Yu
BACKGROUND/AIM: Lenvatinib, a multikinase inhibitor, has become a second-line treatment option for unresectable liver cancer, while its monotherapy response rate is limited. Hence, we aim to investigate whether one of the epigenetic inhibitors will be synthetic lethal with Lenvatinib in liver cancer cells. MATERIALS AND METHODS: We performed high-throughput drug screening in combination with Lenvatinib. And we employed CCK-8-based Bliss Synergy Score analysis, colony formation and western blotting to confirm our screening results in both HepG2 and HCCC9810 cells...
March 28, 2024: Discover. Oncology
#28
JOURNAL ARTICLE
Surgical Intervention After Lenvatinib Treatment in Patients With Advanced Hepatocellular Carcinoma.
Masayuki Okuno, Etsuro Hatano, Masaharu Tada, Takashi Nishimura, Tomohiro Okamoto, Hideaki Sueoka, Kenjiro Iida, Ikuo Nakamura, Hiroko Iijima, Seiko Hirono
BACKGROUND/AIM: The survival and prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who underwent surgical intervention after lenvatinib treatment is not well-understood. PATIENTS AND METHODS: Seventy-six patients with advanced HCC who had lenvatinib treatment were retrospectively analyzed. RESULTS: Of 70 patients who were treated with lenvatinib, 14 patients underwent surgical intervention after lenvatinib treatment for 4-28 weeks...
April 2024: Anticancer Research
#29
JOURNAL ARTICLE
Oneeb Majid, Seiichi Hayato, Sree Harsha Sreerama Reddy, Bojan Lalovic, Taro Hihara, Taisuke Hoshi, Yasuhiro Funahashi, Jagadeesh Aluri, Osamu Takenaka, Sanae Yasuda, Ziad Hussein
Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor (FGF) receptors 1-4, platelet-derived growth factor receptor-α (PDGFRα), KIT, and RET that have been implicated in pathogenic angiogenesis, tumor growth, and cancer. The primary objective of this work was to evaluate, by establishing quantitative relationships, whether lenvatinib exposure and longitudinal serum biomarker data (VEGF, Ang-2, Tie-2, and FGF-23) are predictors for change in longitudinal tumor size which was assessed based on data from 558 patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) receiving either lenvatinib or placebo treatment...
March 26, 2024: CPT: Pharmacometrics & Systems Pharmacology
#30
JOURNAL ARTICLE
Masahiro Kurokawa, Daiki Ikarashi, Renpei Kato, Mitsugu Kanehira, Takashi Fukagai, Wataru Obara
Pancreatic injury is a rare, but noted complication of nephrectomy. We report a case involving a 56-year-old man who presented with cT3bN0M0 left locally advanced renal cell carcinoma with an inferior vena cava thrombus. Nephrectomy with thrombectomy was performed given the remarkable shrinkage of the primary tumor and thrombus following lenvatinib plus pembrolizumab administration. The patient developed postoperative pancreatitis associated with unrecognized minor pancreatic injury, which was treated conservatively...
April 2024: International cancer conference journal
#31
JOURNAL ARTICLE
Zhe Yu, Jing Luo, Hongshan Wei
PURPOSE: The primary aim of this study was to closely monitor and identify adverse events (AEs) linked to lenvatinib, a pharmacotherapeutic agent employed for the management of renal cell carcinoma, thyroid cancer, and hepatocellular carcinoma. The ultimate goal was to optimize patient safety and provide evidence-based guidance for the appropriate utilization of this medication. METHODS: A comprehensive collection and analysis of reports from the FDA Adverse Event Reporting System (FAERS) database was conducted, encompassing the period from the first quarter of 2015 to the first quarter of 2023...
March 30, 2024: Heliyon
#32
REVIEW
Angelika M Starzer, Ladislaia Wolff, Petar Popov, Barbara Kiesewetter, Matthias Preusser, Anna S Berghoff
Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have gained therapeutical significance in cancer therapy over the last years. Due to the high efficacy of each substance group, additive or complementary effects are considered, and combinations are the subject of multiple prospective trials in different tumor entities. The majority of available data results from clinical phase I and II trials. Although regarded as well-tolerated therapies ICI-TKI combinations have higher toxicities compared to monotherapies of one of the substance classes and some combinations were shown to be excessively toxic leading to discontinuation of trials...
March 15, 2024: Cancer Treatment Reviews
#33
REVIEW
Shan Wang, Hongwei Lv, Jing Yu, Miao Chen
BACKGROUND: In the realm of metastatic renal cell carcinoma (mRCC), the introduction of immune checkpoint inhibitors (ICIs) has revolutionized treatment paradigms. Despite their effectiveness, the comprehensive safety profile of these therapies remains inadequately explored. This network meta-analysis aims to comparing the safety profiles of ICI-based treatments in mRCC, offering vital insights that could lead to the optimization of treatment strategies and improvement of patient care...
March 21, 2024: International Immunopharmacology
#34
JOURNAL ARTICLE
Margherita Rimini, Bernardo Stefanini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Fabian Finkelmeier, Changhoon Yoo, José Presa, Elisabeth Amadeo, Virginia Genovesi, Maria Caterina De Grandis, Massimo Iavarone, Fabio Marra, Francesco Foschi, Emiliano Tamburini, Federico Rossari, Francesco Vitiello, Linda Bartalini, Caterina Soldà, Francesco Tovoli, Caterina Vivaldi, Sara Lonardi, Marianna Silletta, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Vera Himmelsbach, Margarida Montes, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Mara Persano, Silvia Camera, Silvia Foti, Luca Aldrighetti, Stefano Cascinu, Andrea Casadei-Gardini, Fabio Piscaglia
INTRODUCTION: Overweight is a negative prognostic factor in the general population in the long term. However, the role of body mass index (BMI) in the short-mid term in advanced tumours is unclear. The present analysis investigates the role of BMI weight classes in a large sample of patients affected by HCC and receiving atezolizumab plus bevacizumab or lenvatinib as first-line treatment. METHODS AND MATERIAL: The cohort included consecutive patients affected by BCLC-c and BCLC-B HCC patients from a multicenter international study group who received atezolizumab plus bevacizumab or lenvatinib as first-line therapy...
March 22, 2024: Liver International: Official Journal of the International Association for the Study of the Liver
#35
JOURNAL ARTICLE
Hong-Xiao Wu, Xiao-Yan Ding, Ya-Wen Xu, Ming-Hua Yu, Xiao-Mi Li, Na Deng, Jing-Long Chen
BACKGROUND: Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses. AIM: To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT. METHODS: From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital...
February 28, 2024: World Journal of Gastroenterology: WJG
#36
JOURNAL ARTICLE
Inês L Damásio, Ana Figueiredo, Joana Maciel, Mariana Horta, Tiago N Silva, Joana Simões-Pereira, Sara Donato, Valeriano Leite
BACKGROUND: Treatment of advanced differentiated thyroid carcinoma (DTC) remains a challenge as 25-50% of patients with locally invasive or distant metastatic disease become refractory to radioiodine (RAI) therapy. Tyrosine kinase inhibitors (TKI) are increasingly used in this setting. The SELECT trial demonstrated that lenvatinib, a multikinase inhibitor, significantly improved progression free survival (PFS) compared to placebo. Our aim was to report the effectiveness and safety of lenvatinib in our series of patients with advanced DTC...
March 21, 2024: Minerva endocrinology
#37
JOURNAL ARTICLE
T Al-Toubah, M J Schell, B Morse, M Haider, T Valone, J Strosberg
BACKGROUND: Immune checkpoint inhibitors (CPIs) have not been shown to be active in well-differentiated neuroendocrine tumors (NETs), with response rates <5%. Lenvatinib is a multitargeted tyrosine kinase inhibitor which binds to vascular endothelial growth factor and fibroblast growth factor receptors and has demonstrated efficacy in pancreatic and gastrointestinal NETs [44% and 16% objective radiographic response rate (ORR), respectively]. The combination of antiangiogenic and CPI therapies can be synergistic...
March 19, 2024: ESMO Open
#38
Bo Zhou, Canyang Zhan, Yang Tian, Zhenzhen Gao, Sheng Yan
BACKGROUND: Malignant Triton tumor (MTT) is a relatively rare subtype of malignant peripheral nerve sheath tumor (MPNST) characterized by rhabdomyosarcoma differentiation. There are no distinct features of MTT, and it is easy to misdiagnose preoperatively. CASE PRESENTATION: Here, we describe a rare case of primary hepatic MTT in a 56-year-old male who presented with nonspecific abdominal pain for 1 day. Magnetic resonance imaging and abdominal computed tomography revealed an extremely large mass located in the right liver with intratumoral hemorrhage, arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging and the possibility of intrahepatic metastasis...
2024: Frontiers in Medicine
#39
JOURNAL ARTICLE
John D Gordan, Erin B Kennedy, Ghassan K Abou-Alfa, Eliza Beal, Richard S Finn, Terence P Gade, Laura Goff, Shilpi Gupta, Jennifer Guy, Hang T Hoang, Renuka Iyer, Ishmael Jaiyesimi, Minaxi Jhawer, Asha Karippot, Ahmed O Kaseb, R Kate Kelley, Jeremy Kortmansky, Andrea Leaf, William M Remak, Davendra P S Sohal, Tamar H Taddei, Andrea Wilson Woods, Mark Yarchoan, Michal G Rose
PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base...
March 19, 2024: Journal of Clinical Oncology
#40
JOURNAL ARTICLE
Vincenzo Marotta, Domenico Rocco, Anna Crocco, Maria Grazia Deiana, Ruggero Martinelli, Francesca Di Gennaro, Mariafelicia Valeriani, Luca Valvano, Alessia Caleo, Luciano Pezzullo, Antongiulio Faggiano, Mario Vitale, Salvatore Monti
CONTEXT: Lenvatinib is approved for the treatment of radioiodine-refractory differentiated thyroid cancer (RR-DTC). The definition of predictive factors of survival is incomplete. OBJECTIVE: To identify pre- and post- treatment survival predictors in a real-life cohort of RR-DTC treated with lenvatinib. DESIGN: Multicenter, retrospective, cohort study. SETTING: Three Italian thyroid cancer referral centers. PARTECIPANTS: 55 RR-DTC treated with lenvatinib...
March 19, 2024: Journal of Clinical Endocrinology and Metabolism
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