Article
Oncology
Jingkai Sun, Wenfeng Lin, Chaoming Li, Hideo Ueki, Ruizhi Xue, Takuya Sadahira, Hao Hu, Koichiro Wada, Na Li, Chunxiao Liu, Motoo Araki, Abai Xu, Peng Huang
Summary: Posaconazole inhibits tumor progression in embryonal rhabdomyosarcoma by inducing G0/G1 arrest and autophagy through downregulating Hedgehog signaling pathway, showing promising potential as an anti-tumor agent targeting ERMS.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Qiushuang Ji, Sai Shi, Biao Ma, Weiwei Zhang, Hailong An, Shuai Guo
Summary: A study found that candesartan (CDST), an angiotensin converting enzyme inhibitor, can effectively inhibit the activity of the TMEM16A channel and has inhibitory effects on the proliferation, migration, and apoptosis of lung adenocarcinoma cells, showing promising anti-lung adenocarcinoma activity. Considering that CDST has been used in clinical treatment of hypertension, it may play an important role as a multi-target drug in the future combined treatment of hypertension and lung adenocarcinoma.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Oncology
Ignatios Ioakeim-Skoufa, Natalia Tobajas-Ramos, Enrica Menditto, Mercedes Aza-Pascual-Salcedo, Antonio Gimeno-Miguel, Valentina Orlando, Francisca Gonzalez-Rubio, Ana Fanlo-Villacampa, Carmen Lasala-Aza, Ewelina Ostasz, Jorge Vicente-Romero
Summary: Drug repurposing, which explores the possibility of using existing marketed drugs in new therapeutic indications, has advantages over discovering new substances for medicinal use. This systematic review focuses on randomized controlled clinical trials that evaluate drug repurposing in cancer. It is important to carefully examine drug repurposing possibilities in oncology with well-designed trials, considering factors that could influence prognosis.
Review
Biochemistry & Molecular Biology
Ngoc Minh Nguyen, Jungsook Cho
Summary: This review discusses the importance of the Hedgehog (Hh) signaling pathway in cancer, the emergence of Hh pathway inhibitors, and the mechanisms of drug resistance. Additionally, strategies to overcome resistance are addressed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Obstetrics & Gynecology
Natalia Garcia, Mara Ulin, Mohamed Ali, Ayman Al-Hendy, Katia Candido Carvalho, Qiwei Yang
Summary: The study found that the GLI inhibitor (Gant61) has a strong inhibitory effect on tumor growth in uterine leiomyosarcoma, significantly reducing the expression of Ki67. The GLI inhibitor also suppresses the expression of GLI1, BMP4, and c-MYC, indicating the involvement of the HH signaling pathway in the LMS experimental model.
REPRODUCTIVE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Xin Pan, Teng-yu Mao, Yan-wen Mai, Cheng-cheng Liang, Wei-hao Huang, Yong Rao, Zhi-shu Huang, Shi-liang Huang
Summary: Topo II and Hsp90 have similar structures and can be targeted by the antimalarial drug quinacrine. Quinacrine can specifically bind and inhibit the activities of these two enzymes, and it remains effective against multidrug-resistant and atypical drug-resistant cell lines.
Article
Biochemistry & Molecular Biology
Yijing Tang, Yonglan Liu, Yanxian Zhang, Dong Zhang, Xiong Gong, Jie Zheng
Summary: There is a strong pathological correlation between cardiovascular disease (CVD) and Type II diabetes (T2D), both of which share common risk factors. The study proposed repurposing a CVD drug, cloridarol, as a human islet amyloid peptide (hIAPP) inhibitor to prevent abnormal misfolding and aggregation in T2D. Experimental and computational approaches confirmed the inhibitory activity of cloridarol on hIAPP aggregation and toxicity, providing a potential new treatment approach.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Infectious Diseases
Avril Coghlan, Frederick A. Partridge, Maria Adelaida Duque-Correa, Gabriel Rinaldi, Simon Clare, Lisa Seymour, Cordelia Brandt, Tapoka T. Mkandawire, Catherine Mccarthy, Nancy Holroyd, Marina Nick, Anwen E. Brown, Sirapat Tonitiwong, David B. Sattelle, Matthew Berriman
Summary: Hundreds of millions of people worldwide are infected with the whipworm and current drugs have low efficacy. In this study, we tested drugs approved for other diseases and identified 14 compounds that can effectively kill the whipworm. However, their efficacy in mice was limited due to their chemical properties and pharmacokinetics.
PLOS NEGLECTED TROPICAL DISEASES
(2023)
Article
Medicine, Research & Experimental
Sahar K. Hegazy, Gamal A. El-Azab, Fatma Zakaria, Mohamed F. Mostafa, Reham A. El-Ghoneimy
Summary: This study investigates the anti-tumor activity and safety of mebendazole in patients with mCRC. The results show that mebendazole enhances tumor response to chemotherapy and is well tolerated, suggesting its potential as a candidate for drug repositioning in mCRC.
Article
Biochemistry & Molecular Biology
Seong Bin Jo, So Jung Sung, Hong Seok Choi, Jae-Sung Park, Yong-Kil Hong, Young Ae Joe
Summary: In this study, the authors explored a novel strategy to improve the efficacy of Mebendazole (MBZ) in the treatment of brain tumors. They found that co-treatment with an autophagy inhibitor significantly enhanced the anticancer effects of MBZ and showed enhanced effects in TMZ-resistant glioblastoma cells. The authors suggested that modulating protective autophagy could be an efficient strategy for enhancing the anticancer efficacy of MBZ.
BIOMOLECULES & THERAPEUTICS
(2022)
Review
Biochemistry & Molecular Biology
Daniela Meco, Giorgio Attina, Stefano Mastrangelo, Pierluigi Navarra, Antonio Ruggiero
Summary: Repurposing approved non-antitumor drugs, such as Mebendazole, offers a promising and affordable strategy to increase the number of effective anticancer drugs. Mebendazole has demonstrated anticancer properties and can target multiple cancers. It shows potential as both a monotherapy and in combination with standard chemotherapeutics and radiotherapy. Its repurposing could reduce medical care costs and optimize existing cancer therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Cynthia Vanesa Rivero, Santiago Jose Martinez, Paul Novick, Juan Agustin Cueto, Betiana Nebai Salassa, Maria Cristina Vanrell, Xiaomo Li, Carlos Alberto Labriola, Luis Mariano Polo, David M. Engman, Joachim Clos, Patricia Silvia Romano
Summary: T. cruzi, the causal agent of Chagas disease, poses challenges due to its ability to infect different host cells and its resistance to current treatments. Carvedilol, identified through virtual screening, shows promising in vitro and in vivo activity against T. cruzi, making it a potential lead for Chagas disease treatment.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Chemistry, Medicinal
Liu Yang, Caiwang Yang, Lu Wang, Zhongzheng Yang, Deyin Guo, Chengpeng Fan
Summary: This study identified five known drugs that could inhibit MIF's tautomerase activity and MIF-mediated cell chemotaxis. Compounds D2 (histamine), D5 (metaraminol), and D8 (nebivolol) exhibited micromolar-range inhibition potency close to the positive control ISO-1. The study elucidates the molecular mechanism of repurposed drugs acting on MIF and provides a structural foundation for lead optimization to promote the clinical development of MIF-targeted drugs.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Souvik Banerjee, Shalini Yadav, Sourav Banerjee, Sayo O. Fakayode, Jyothi Parvathareddy, Walter Reichard, Surekha Surendranathan, Foyez Mahmud, Ryan Whatcott, Joshua Thammathong, Bernd Meibohm, Duane D. Miller, Colleen B. Jonsson, Kshatresh Dutta Dubey
Summary: This study utilized pharmacophore and molecular modeling-based screening to identify potential antiviral drugs, with molecular dynamics simulations revealing three drugs with promising interactions with the SARS-CoV-2 M-pro active site. The results suggest Glu166 as an interesting target for structure-based drug design.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Multidisciplinary Sciences
S. Mansoori, M. Fryknas, C. Alvfors, A. Loskog, R. Larsson, P. Nygren
Summary: This study investigated the safety and efficacy of individualized dose adjusted mebendazole in patients with advanced gastrointestinal cancer. While mebendazole was found to be safe and well tolerated, all patients experienced rapid disease progression. Further exploration of mebendazole as an anticancer drug may require new approaches such as prodrug development and combination therapy with other anticancer drugs.
SCIENTIFIC REPORTS
(2021)
Meeting Abstract
Oncology
Z. R. Moore, A. Rimner, S. Lobaugh, A. Geyer, D. Y. Gelblum, A. F. Shepherd, N. Shaverdian, A. J. Wu, J. E. Chaft, M. G. Zauderer, C. M. Rudin, N. Vander Els, M. Chawla, D. R. Jones, D. M. Sopka, R. Mak, Z. Liao, D. R. Gomez, Z. Zhang, P. Paik
ANNALS OF ONCOLOGY
(2022)
Article
Oncology
Paul K. Paik, Pang-Dian Fan, Besnik Qeriqi, Azadeh Namakydoust, Bobby Daly, Linda Ahn, Rachel Kim, Andrew Plodkowski, Ai Ni, Jason Chang, Rachel Fanaroff, Marc Ladanyi, Elisa de Stanchina, Charles M. Rudin
Summary: Increased understanding of the mutational landscape of squamous cell lung cancers (LUSCs) has not resulted in effective targeted therapies. This study investigates the potential of TORC1/2 inhibitor TAK-228 in NSCLC models with NRF2-activating alterations and reports positive outcomes in a phase 2 clinical trial. TAK-228 shows promising single-agent activity in LUSC patients with NRF2 activation and highlights the importance of targeting metabolism in NSCLC.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Review
Oncology
Kenta Kawasaki, Natasha Rekhtman, Alvaro Quintanal-Villalonga, Charles M. Rudin
Summary: The review provides a comprehensive overview of the current understanding of NENs in the gastrointestinal system and lung from both clinical and biological perspectives. The authors discuss the commonalities and organ-specific differences of NENs and advocate for a tissue-agnostic approach to drug development, in order to improve patient care by accelerating research across different disease entities.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Oncology
Noura J. Choudhury, Antonio Marra, Jane S. Y. Sui, Jessica Flynn, Soo-Ryum Yang, Christina J. Falcon, Pier Selenica, Adam J. Schoenfeld, Natasha Rekhtman, Daniel Gomez, Michael F. Berger, Marc Ladanyi, Maria Arcila, Charles M. Rudin, Gregory J. Riely, Mark G. Kris, Glenn Heller, Jorge S. Reis-Filho, Helena A. Yu
Summary: The study explores the potential of identifying and intervening on molecular markers associated with therapeutic resistance to improve patient outcomes in metastatic EGFR-mutant lung cancer treated with first-line osimertinib. Baseline atypical EGFR and concurrent TP53/RB1 alterations are associated with shorter progression-free survival on first-line osimertinib. Tissue-based genomic analysis allows for treatment adaptation based on identified mechanisms of resistance at the time of progression, leading to improved postprogression survival.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Oncology
Charles M. Rudin, Hardev S. Pandha, Matthew Zibelman, Wallace L. Akerley, Kevin J. Harrington, Daphne Day, Andrew G. Hill, Steven J. O'Day, Timothy D. Clay, Gavin M. Wright, Ross R. Jennens, David E. Gerber, Jonathan E. Rosenberg, Christy Ralph, David C. Campbell, Brendan D. Curti, Jaime R. Merchan, Yixin Ren, Emmett Schmidt, Lisa Guttman, Sumati Gupta
Summary: This study evaluated the efficacy and safety of V937 combined with pembrolizumab in patients with advanced solid tumors. The results showed that the combination therapy had a manageable safety profile, but did not achieve greater efficacy than pembrolizumab monotherapy in non-small cell lung cancer and urothelial cancer.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Editorial Material
Oncology
Salomon Tendler, Charles M. Rudin
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Charles M. M. Rudin, Martin Reck, Melissa L. L. Johnson, Fiona Blackhall, Christine L. L. Hann, James Chih-Hsin Yang, Julie M. M. Bailis, Gwyn Bebb, Amanda Goldrick, John Umejiego, Luis Paz-Ares
Summary: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine carcinoma with limited treatment options. DLL3, a Notch inhibitory ligand, is overexpressed on SCLC cells, making it an attractive therapeutic target. This article discusses the clinical experience with a DLL3-targeting antibody-drug conjugate called Rova-T, as well as other DLL3-targeting agents currently in development, including T-cell engager molecules and CAR T-cell therapy. The challenges and opportunities for DLL3-targeting therapies, such as using DLL3 as a biomarker and exploring combinatorial approaches, are also discussed.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Oncology
Charles M. Rudin, David Balli, W. Victoria Lai, Allison L. Richards, Evelyn Nguyen, Jacklynn Egger, Noura J. Choudhury, Triparna Sen, Andrew Chow, John T. Poirier, William J. Geese, Matthew D. Hellmann, Ann Forslund
Summary: A study found that antigen presentation machinery signature and infiltrating CD8 T cells were correlated with survival in SCLC patients treated with nivolumab, suggesting their potential as biomarkers for predicting immunotherapy efficacy. The study also identified the association between durable benefit from immunotherapy and antigen processing and presentation.
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Immunology
Ariella Glasner, Samuel A. Rose, Roshan Sharma, Herman Gudjonson, Tinyi Chu, Jesse A. Green, Sham Rampersaud, Izabella K. Valdez, Emma S. Andretta, Bahawar S. Dhillon, Michail Schizas, Stanislav Dikiy, Alejandra Mendoza, Wei Hu, Zhong-Min Wang, Ojasvi Chaudhary, Tianhao Xu, Linas Mazutis, Gabrielle Rizzuto, Alvaro Quintanal-Villalonga, Parvathy Manoj, Elisa de Stanchina, Charles M. Rudin, Dana Pe'er, Alexander Y. Rudensky
Summary: Traditional roles of regulatory T (T-reg) cells as suppressors of antigen presenting cells and effector T cells have expanded to include tissue maintenance functions, suggesting a broader regulatory role than previously thought. In lung cancer and injury-induced inflammation, T-reg cell depletion led to changes in gene expression in fibroblasts, endothelial and myeloid cells, involving VEGF and CCR2 signaling. Combined T-reg cell depletion and short-term VEGF blockade showed improved control of PD-1 blockade-resistant lung adenocarcinoma progression, highlighting the potential of combination therapies for solid organ cancers.
Editorial Material
Oncology
Charles M. Rudin
Article
Oncology
Subhamoy Chakraborty, Charles Coleman, Parvathy Manoj, Deniz Demircioglu, Nisargbhai Shah, Elisa de Stanchina, Charles M. Rudin, Dan Hasson, Triparna Sen
Summary: Lurbinectedin significantly reduces cell viability in most SCLC models, with the best response observed in POU2F3-driven SCLC cells. We also found that lurbinectedin, either as a single agent or in combination with osimertinib, shows an appreciable antitumor response in EGFR-mutant lung adenocarcinoma models with histologic transformation to SCLC. Transcriptomic analysis revealed the induction of apoptosis, repression of epithelial-mesenchymal transition, and modulation of PI3K/AKT, NOTCH signaling associated with lurbinectedin response in both de novo and transformed SCLC models.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Joy A. Pai, Matthew D. Hellmann, Jennifer L. Sauter, Marissa Mattar, Hira Rizvi, Hyung Jun Woo, Nisargbhai Shah, Evelyn M. Nguyen, Fathema Z. Uddin, Alvaro Quintanal-Villalonga, Joseph M. Chan, Parvathy Manoj, Viola Allaj, Marina K. Baine, Umesh K. Bhanot, Mala Jain, Irina Linkov, Fanli Meng, David Brown, Jamie E. Chaft, Andrew J. Plodkowski, Mathieu Gigoux, Helen H. Won, Triparna Sen, Daniel K. Wells, Mark T. A. Donoghue, Elisa de Stanchina, Jedd D. Wolchok, Brian Loomis, Taha Merghoub, Charles M. Rudin, Andrew Chow, Ansuman T. Satpathy
Summary: Paired scRNA/TCR-seq analysis of T cells from NSCLC patients after ICB reveals clonally linked TFH and tumor-specific CD8+ T cells in tumor draining LNs. Exhausted CD8+ T cells, Treg, and TFH cells show progressive exhaustion trajectories with proximity to the tumor microenvironment. Longitudinal tracking demonstrates the persistence of tumor-specific T cell clones in peripheral blood for years after ICB therapy.
Article
Medicine, Research & Experimental
Janneke E. Jaspers, Jonathan F. Khan, William D. Godfrey, Andrea Lopez, Metamia Ciampricotti, Charles M. Rudin, Renier J. Brentjens
Summary: This study developed a chimeric antigen receptor (CAR) against DLL3 and demonstrated its antitumor efficacy in xenograft and murine SCLC models. CAR T cell expression of IL-18 enhanced the potency of DLL3-targeting CAR T cell therapy and increased the activation of CAR T cells and tumor-infiltrating lymphocytes. Human IL-18-secreting anti-DLL3 CAR T cells showed durable responses in multiple SCLC models, and this effect could be further enhanced with anti-PD-1 blockade.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Laura Boucai, Federico Salas-Lucia, Gnana P. Krishnamoorthy, Eric Sherman, Charles M. Rudin, Alexander Drilon, Antonio C. Bianco, James A. Fagin
Summary: This study investigated the mechanisms of selpercatinib-induced thyroid dysfunction in RET-mutant MTC and NSCLC patients. The study found that selpercatinib had a nontranscriptional effect on D2 activity, leading to a reduction in T3 levels, primarily observed in patients without a thyroid. Supplementing Liothyronine restored normal thyroid function.
JCO PRECISION ONCOLOGY
(2022)
Meeting Abstract
Oncology
Alvaro Quintanal-Villalonga, Hirokazu Taniguchi, Yuan Hao, Andrew Chow, Yingqian A. Zhan, Umesh Bhanot, Juan Qiu, Elisa de Stanchina, Richard P. Koche, John T. Poirier, Charles M. Rudin
JOURNAL OF CLINICAL ONCOLOGY
(2022)