tbuckley/cabot-search huggingface dataset:
Safety, Efficacy and Biomarker Analysis of Crizotinib in MET Mutated Non-Small Cell Lung Cancer – Results from the Drug Rediscovery Protocol
Authors: Karlijn Verkerk, Tijmen J.W.T. van der Wel, Laurien J. Zeverijn, Birgit S. Geurts, Ilse A.C. Spiekman, Gijs F. de Wit, Paul Roepman, Anne M.L. Jansen, Vincent van der Noort, Egbert F. Smit, Ann Hoeben, Lizza E.L. Hendriks, Michel M. Van den Heuvel, Berber Piet, Gerarda J.M. Herder, Sayed M.S. Hashemi, Hans Gelderblom, Henk M.W. Verheul, Emile E. Voest, Adrianus J. de Langen
Journal: Clinical Cancer Research (2024)

Abstract Background. MET mutations occur in 3-4% of advanced non-small cell lung cancer (aNSCLC), correlating with poor survival. Despite known sensitivity of MET mutated (METmut) aNSCLC to c-MET-inhibition, no approved therapies existed until 2022. Methods. In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping (METex14) or other METmuts received crizotinib 250 mg BID until disease progression or intolerable toxicity. Primary endpoints were clinical benefit (CB: RECIST v1.1 confirmed partial response (PR), complete response (CR) or stable disease (SD) ≥16 weeks) and safety. Patients were enrolled using a Simon-like two-stage design, with eight patients in stage 1 and if ≥1/8 patients had CB, 24 patients in stage 2. Whole genome and RNA-sequencing were performed on baseline biopsies. Results. Between 09/2018 and 10/2022, 30 patients started treatment, and 24 were response-evaluable after completing ≥1 full treatment cycle. Two patients (8.3%) achieved CR, thirteen (54.2%) PR and two (8.3%) SD. The CB-rate was 70.8% (95%CI 48.9-87.4) and the objective response rate was 62.5% (95%CI 40.6-81.2). After 21.2 months median follow-up, median duration of response, progression-free and overall survival were 9.3 (95%CI 6.5-NA), 10.2 (95%CI 6.0-20.1) and 13.0 months (95%CI 9.0-NA), respectively. Twenty-three treatment-related grade ≥3 adverse events occurred in 12/30 patients (40%), causing treatment-discontinuation in three (10%). One patient (achieving CR) had a tyrosine kinase domain mutation (p.H1094Y), all other patients had METex14. Conclusions. Crizotinib is a valuable treatment option in METmut aNSCLC.
Phase 2 trial of regorafenib in recurrent or metastatic adenoid cystic carcinoma
Authors: Antoine Desilets, Joris L. Vos, Nora Katabi, Fengshen Kuo, Zaineb Nadeem, Maximilian Linxweiler, Irina Ostrovnaya, Shrujal Baxi, Lara A. Dunn, Eric J. Sherman, David G. Pfister, Luc G.T. Morris, Alan L. Ho
Journal: Clinical Cancer Research (2024)

Abstract Background: There is a significant need for effective therapies to treat recurrent/metastatic (R/M) adenoid cystic carcinoma (ACC). This study evaluated the multi-targeted, vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) regorafenib in patients with R/M ACC. Methods: Patients with progressive R/M ACC were treated with regorafenib until disease progression, consent withdrawal, or excessive toxicity. The primary endpoints were best overall response (BOR) and 6-month progression-free survival (PFS). Genomic and transcriptomic biomarker analyses were performed in tumors from trial participants. Results: Thirty-eight patients were enrolled, including 7 (18%) patients with prior VEGFR-TKIs. No objective responses were observed. Six-month PFS was 45%, and median PFS was 7.2 months (95%CI 5.2-11.9 months). Presence of either activating NOTCH1 (22%) or KDM6A alterations (24%) was associated with decreased PFS (HR 2.6, 95%CI 1.1-6.1, p=0.03). Bulk RNA sequencing of pre-treatment tumors revealed that regorafenib clinical benefit (CB; PFS≥6 months; n=11) was associated with native enrichment of immune-related signatures. Immune deconvolution revealed a greater degree of macrophage and T-cell infiltration in CB tumors. Tumors from patients with no clinical benefit (NCB; PFS&amp;lt;6 months; n=9) had greater expression of signatures related to cell cycle progression (E2F targets, G2/M checkpoint). Conclusion: The trial failed to meet the pre-specified 6-month PFS and BOR targets. We hypothesize that TKI efficacy may be reliant upon an interplay between kinase inhibition and the ACC immune microenvironment, while programs promoting cell cycle progression may contribute to TKI resistance. These observations suggest that trials evaluating CDK4/6 inhibition plus a VEGFR-TKI should be considered.
Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy
Authors: Kua Liu, Lingkai Kong, Huawei Cui, Louqian Zhang, Qilei Xin, Yan Zhuang, Ciliang Guo, Yongzhong Yao, Jinqiu Tao, Xiaosong Gu, Chunping Jiang, Junhua Wu
Journal: Cell Reports Medicine (2024)
HumanIslets.com: Improving accessibility, integration, and usability of human research islet data
Authors: Jessica D Ewald, Yao Lu, Cara E Ellis, Jessica Worton, Jelena Kolic, Shugo Sasaki, Dahai Zhang, Theodore Dos Santos, Aliya F Spigelman, Austin Bautista, Xiao-Qing Dai, James G Lyon, Nancy P Smith, Jordan M Wong, Varsha Rajesh, Han Sun, Seth A Sharp, Jason C Rogalski, Renata Moravcova, Haoning H Cen, Jocelyn E Manning Fox, Ella Atlas, Jennifer E Bruin, Erin E Mulvihill, C Bruce Verchere, Leonard J Foster, Anna L Gloyn, James D Johnson, Andrew R Pepper, Francis C Lynn, Jianguo Xia, Patrick E MacDonald
Journal: Cell Metabolism (2024)
Two decades of advances in clinical oncology — lessons learned and future directions
Authors: Susana Banerjee, Christopher M Booth, Eduardo Bruera, Markus W Büchler, Alexander Drilon, Terry J Fry, Irene M Ghobrial, Luca Gianni, Rakesh K Jain, Guido Kroemer, Josep M Llovet, Georgina V Long, Klaus Pantel, Kathy Pritchard-Jones, Howard I Scher, Josep Tabernero, Ralph R Weichselbaum, Michael Weller, Yi-Long Wu
Journal: Nature Reviews Clinical Oncology (2024)
The triple A (AAA) model globally recapitulates adverse outcomes in essential thrombocythemia
Authors: Luca Tosoni, Gian Luca Morelli, Gaia Tomadini, Davide Lazzarotto, Carla Filì, Erica Simeone, Maria Elena Zannier, Chiara Callegari, Matteo Fanin, Giulia Battaglia, Melissa Bergnach, Daniela Damiani, Renato Fanin, Mario Tiribelli
Journal: Blood Cancer Journal (2024)
A Robust ROS Generation and Ferroptotic Lipid Modulation Nanosystem for Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy
Authors: Chao Jiang, Wenxi Li, Jie Yan, Xinying Yu, Yuzhao Feng, Bei Li, Yuan Liu, Yunlu Dai
Journal: Advanced Healthcare Materials (2024)

Abstract Ferroptosis initiation is often utilized for synergistic immunotherapy. While, current immunotherapy is limited by an immunosuppressive tumor microenvironment (TME), and ferroptosis is limited by insufficient reactive oxygen species (ROS) and ferroptotic lipids in tumor cells. Here, an arachidonic acid (AA) loaded nanosystem (CTFAP) is developed to mutually reinforce ferroptosis and cancer immunotherapy by augmenting ROS generation and modulating ferroptotic lipids. CTFAP is composed of acid‐responsive core calcium peroxide (CaO 2 ) nanoparticles, ferroptotic lipids sponsor AA, tetracarboxylic porphyrin (TCPP) and Fe 3+ based metal‐organic framework structure, and biocompatible mPEG‐DSPE for improved stability. Once endocytosed by tumor cells, CTFAP can release oxygen (O 2 ) and hydrogen peroxide (H 2 O 2 ) in the acidic TME, facilitating TCPP‐based sonodynamic therapy and Fe 3+ ‐mediated Fenton‐like reactions to generate substantial ROS for cell ferroptosis initiation. The immunogenic cell death (ICD) after ferroptosis promotes interferon γ (IFN‐γ) secretion to up‐regulate the expression of long‐chain family member 4 (ACSL4), cooperating with the released AA from CTFAP to accelerate the accumulation of lipid peroxidation (LPO) and thereby promoting ferroptosis in cancer cells.CTFAP with ultrasound treatment efficiently suppresses tumor growth, has great potential to challenges in cancer immunotherapy.
Publisher Correction: Integrative proteogenomic profiling of high-risk prostate cancer samples from Chinese patients indicates metabolic vulnerabilities and diagnostic biomarkers
Authors: Baijun Dong, Jun-Yu Xu, Yuqi Huang, Jiacheng Guo, Qun Dong, Yanqing Wang, Ni Li, Qiuli Liu, Mingya Zhang, Qiang Pan, Hanling Wang, Jun Jiang, Bairun Chen, Danqing Shen, Yiming Ma, Linhui Zhai, Jian Zhang, Jing Li, Wei Xue, Minjia Tan, Jun Qin
Journal: Nature Cancer (2024)
Early integration of palliative care versus standard cardiac care for patients with heart failure (EPCHF): a multicentre, parallel, two-arm, open-label, randomised controlled trial
Authors: Mahmoud Balata, Lukas Radbruch, Michaela Hesse, Ralf Westenfeld, Martin Neukirchen, Roman Pfister, Yann-Nicolas Batzler, Can Öztürk, Refik Kavsur, Vedat Tiyerili, Birgitta Weltermann, Robert Pölsler, Thomas Standl, Georg Nickenig, Marc Ulrich Becher
Journal: The Lancet Healthy Longevity (2024)
C‐<scp>CAR066</scp>, a novel fully human anti‐<scp>CD20 CAR</scp>‐T therapy for relapsed or refractory large B‐cell lymphoma after failure of anti‐<scp>CD19 CAR</scp>‐T therapy: A phase I clinical study
Authors: Ping Li, Wei Liu, Lili Zhou, Shiguang Ye, Dan Zhu, Jiaqi Huang, Jing Li, Chengxiao Zheng, Shigui Zhu, Xin Yao, Kevin Zhu, Yihong Yao, Lugui Qiu, Aibin Liang, Dehui Zou
Journal: American Journal of Hematology (2024)

Managing large B-cell lymphoma (LBCL) that is refractory to or relapsed after chimeric antigen receptor (CAR)-T therapy remains a significant challenge. Here we aimed to investigate the safety and efficacy of C-CAR066, an autologous fully human anti-CD20 specific CAR-T, for relapsed/refractory LBCL after failure of anti-CD19 CAR-T therapy. This first-in-human, single-arm, phase 1 study was conducted at two sites in China. Eligible patients had to be histologically confirmed with CD20-positive LBCL and must have received prior anti-CD19 CAR-T therapy. Patients received a single intravenous infusion of C-CAR066 at a target dose of 2.0 × 10