Article
Immunology
Feifei Nan, Xiaorui Fu, Xinfeng Chen, Ling Li, Xin Li, Jingjing Wu, Xiaoyan Feng, Xiaolong Wu, Jiaqin Yan, Mingzhi Zhang
Summary: CAR-T cell therapy has revolutionized the treatment of malignant tumors, but resistance to this treatment is still a challenge. In this study, three lymphoma patients resistant to CAR-T cell therapy were analyzed retrospectively and it was found that pembrolizumab, 21D4 CAR-T cells, and ibrutinib plus venetoclax may be effective in overcoming treatment resistance.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Dongha Kim, Hye Jin Nam
Summary: PARP inhibitors, the first clinically approved drugs based on synthetic lethality, have shown promising outcomes in the treatment of cancer patients. Resistance development remains a challenge, but efforts are being made to overcome it and enhance the efficacy of PARP inhibitors. Mechanisms of action, causes of resistance, and innovative attempts to degrade PARP proteins are discussed in this study.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Syed Nasir Abbas Bukhari
Summary: A key issue in modern cancer treatment is the resistance to conventional chemotherapy and targeted medicines. Cancer nanotherapeutics aim to overcome these limitations and provide effective treatment through the use of nanoparticulate delivery systems. Various strategies such as passive and active targeting, nano-drug, and combination therapy have shown promising results. However, the complexity of tumor biology and limited understanding of nano-bio interactions hinder the clinical translation and commercialization of cancer nanotherapeutics.
Review
Biology
Giulia Mitola, Paolo Falvo, Francesco Bertolini
Summary: Drug resistance-induced disease relapse is still a major clinical challenge in cancer treatment. Tumor cells may develop resistant cells or minimal residual disease cells which can lead to secondary tumors. Therefore, eradication of MRDs is crucial to prevent tumor relapse, and several research groups are focused on understanding the origin, characteristics, and eradication of MRDs.
Review
Oncology
Elena Diaz-Rodriguez, Lucia Gandullo-Sanchez, Alberto Ocana, Atanasio Pandiella
Summary: A proportion of breast tumors carry the oncogenic HER2 protein, and while therapies targeting HER2 have shown efficacy, resistance remains a significant clinical issue. The emergence of antibody-drug conjugates (ADCs) has provided a new category of antitumor agents for HER2+ breast tumors. With two FDA-approved anti-HER2 ADCs in clinical use and others in development, there is hope for improving outcomes and overcoming resistance in HER2-positive breast cancer patients.
Article
Cardiac & Cardiovascular Systems
Nhat Giang Minh, Hai Nguyen Hoang, Daichi Maeda, Yuya Matsue
Summary: This study aims to demonstrate the effectiveness of early tolvaptan add-on therapy in patients with acute heart failure and renal dysfunction, and to provide clinical evidence of loop diuretic resistance.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Yang-Yang Gao, Wei-Cheng Yang, Charles R. Ashby Jr, Ge-Fei Hao
Summary: The emergence of drug resistance poses a major challenge in chemotherapy. Targeting cryptic binding sites (CBSs) with specific drugs offers a novel approach to overcome drug resistance. In this short communication, we explain and discuss the potential of CBS discovery and inhibitor development in addressing drug resistance.
DRUG RESISTANCE UPDATES
(2023)
Review
Biochemistry & Molecular Biology
Robert H. Guirguis, Leonard P. Tan, Rebecca M. Hicks, Aniqa Hasan, Tina D. Duong, Xia Hu, Jordan Y. S. Hng, Mohammad H. Hadi, Henry C. Owuama, Tamara Matthyssen, Michael McCullough, Federica Canfora, Rita Paolini, Antonio Celentano
Summary: Invasive dental treatment in patients taking antiresorptive and antiangiogenic drugs may lead to medication-related osteonecrosis of the jaw (MRONJ). However, the exact pathogenesis of this disease is still unclear. This study reviewed in vitro studies and found that these drugs have cytotoxic effects on oral cells.
Article
Chemistry, Medicinal
Oliver Kraft, Anne-Kathrin Hartmann, Sarah Brandt, Sophie Hoenke, Niels V. Heise, Rene Csuk, Thomas Mueller
Summary: Amides and rhodamine B conjugates of pentacyclic triterpene acids have demonstrated excellent cytotoxicity against human tumor cells. The spacer attached to the carboxyl group at ring E determines the cytotoxicity of these conjugates. One acetylated homopiperazinyl spacered rhodamine B conjugate showed high cytotoxicity against ovarian carcinoma cells. These conjugates act as mitocans and induce apoptosis, and have the ability to overcome resistance to standard chemotherapeutic drugs, making them promising candidates for chemotherapy.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Pharmacology & Pharmacy
Josef Jampilek
Summary: Infections pose an escalating global threat due to the alarming rise in resistant microbial pathogens. This review summarizes the causes of antimicrobial resistance, discusses various approaches to the discovery of new anti-infective drugs, and focuses on the strategy of drug repurposing, offering critical remarks on the repurposing of non-antibiotics. A comprehensive overview of drugs tested for their antimicrobial activity is provided to support existing anti-infective therapeutics.
DRUG DISCOVERY TODAY
(2022)
Article
Oncology
Cassandra S. L. Ho, Alicia Tuens, Hans-Ulrich Schildhaus, Marcel Wiesweg, Barbara M. Gruener, Balazs Hegedus, Martin Schuler, Alexander Schramm, Sebastian Oeck
Summary: The study demonstrates that HER2 copy number gain is a clinically relevant resistance mechanism to pharmacological KRASG12C inhibition in lung cancer patients. Co-targeting SHP2 can overcome this resistance mechanism effectively.
EUROPEAN JOURNAL OF CANCER
(2021)
Review
Pharmacology & Pharmacy
Meng Liu, Shan Gao, Reham M. Elhassan, Xuben Hou, Hao Fang
Summary: SHP2, encoded by PTPN11, is widely recognized as a carcinogenic phosphatase and a promising anti-cancer drug target. It regulates multiple signaling pathways and immune cell function, and has shown therapeutic potential in overcoming drug resistance in cancer treatment.
ACTA PHARMACEUTICA SINICA B
(2021)
Review
Pharmacology & Pharmacy
Zhenwei Su, Shaowei Dong, Shan-Chao Zhao, Kaisheng Liu, Yao Tan, Xingyu Jiang, Yehuda G. Assaraf, Bo Qin, Zhe-Sheng Chen, Chang Zou
Summary: Chemotherapy is powerful in eliminating malignant cells, but its efficacy is often hindered by drug resistance. Nanomedicine, focusing on targeted drug delivery to tumor tissues using nano-sized formulations, shows promise in improving treatment outcomes, minimizing adverse effects, and overcoming cancer drug resistance. This approach involves strategies such as passive and active targeted delivery, delivering multidrug combinations, and multimodal combination therapy to pave the way for effective cancer treatment and holds great potential in overcoming drug resistance.
DRUG RESISTANCE UPDATES
(2021)
Review
Pharmacology & Pharmacy
Catherine Passirani, Anne Vessieres, Giuseppe La Regina, Wolfgang Link, Romano Silvestri
Summary: Identifying and validating proteins involved in resistance mechanisms is crucial for innovative therapeutic strategies to improve the clinical outcome of cancer patients. Rational treatment strategies targeting transcription factors, pseudokinases, nuclear export receptors, and immunogenic cell death show promise in overcoming therapy resistance. The success in inhibiting specific proteins and pathways implicated in drug resistance illustrates the potential of targeted therapies and immunotherapies to improve clinical outcomes.
DRUG RESISTANCE UPDATES
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Wei Zou, Alyssa McAdorey, Hongbin Yan, Wangxue Chen
Summary: The translation of antibacterial nanoparticles into nanomedicine requires a deep understanding of their dynamic nature and how they overcome immunological and biological barriers. Nanomedicines need to have prolonged serum stability through stealth coating or protein corona formation to prevent rapid clearance by the immune system. A preferred nanoparticle formulation may include nonimmunogenic carbohydrates that act as both stealth coatings and ligands of specific endothelial receptors, facilitating their crossing of the vascular barrier. This enables more rapid delivery and accumulation at infection sites, leading to broader and faster clinical responses than targeting bacterial surface receptors. Ideally, antibacterial nanomedicines should be able to penetrate biofilms through fusion and/or diffusion for targeted delivery.
Article
Oncology
Antoine Italiano, Philippe A. Cassier, Chia-Chi Lin, Tuomo Alanko, Katriina J. Peltola, Anas Gazzah, Her-Shyong Shiah, Emiliano Calvo, Andres Cervantes, Desamparados Roda, Diego Tosi, Bo Gao, Michael Millward, Lydia Warburton, Minna Tanner, Stefan Englert, Stacie Lambert, Apurvasena Parikh, Daniel E. Afar, Gregory Vosganian, Victor Moreno
Summary: This study presents the safety, efficacy, pharmacokinetic, and pharmacodynamic data of budigalimab in head and neck squamous cell carcinoma and non-small cell lung cancer patients. Results showed that the drug's profiles are similar to other PD-1 inhibitors, and development in combination with novel anticancer agents is ongoing. The objective response rates and median progression-free survival varied slightly between the HNSCC and NSCLC cohorts.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2022)
Article
Oncology
Jennifer R. Diamond, Valentina Boni, Emerson Lim, Grzegorz Nowakowski, Raul Cordoba, Daniel Morillo, Ray Valencia, Isabelle Genvresse, Claudia Merz, Oliver Boix, Melanie M. Frigault, Joy M. Greer, Ahmed M. Hamdy, Xin Huang, Raquel Izumi, Harvey Wong, Victor Moreno
Summary: This study reports the first-in-human phase I study of VIP152, a highly selective cyclin-dependent kinase 9 (CDK9) inhibitor. The results show that VIP152 monotherapy demonstrated a favorable safety profile and evidence of clinical benefit in patients with advanced high-grade B-cell lymphoma and solid tumors.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Robert Jones, Ruth Plummer, Victor Moreno, Louise Carter, Desamparados Roda, Elena Garralda, Rebecca Kristeleit, Debashis Sarker, Tobias Arkenau, Patricia Roxburgh, Harriet S. Walter, Sarah Blagden, Alan Anthoney, Barbara J. Klencke, Mark M. Kowalski, Udai Banerji
Summary: The purpose of this study was to assess the safety, recommended dose, pharmacokinetic profile, and clinical activity of the novel checkpoint kinase 1 (Chk1) inhibitor SRA737 in combination with gemcitabine in patients with advanced solid tumors. The results showed that the combination of SRA737 and low-dose gemcitabine was well tolerated and demonstrated tumor responses in anogenital cancer and other solid tumors.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Victor Moreno, Ruth Perets, Tamar Peretz-Yablonski, Nele Fourneau, Suzette Girgis, Yue Guo, Peter Hellemans, Raluca Verona, Natalia Pendas, Qi Xia, Ravit Geva, Emiliano Calvo
Summary: Mitazalimab, a human monoclonal antibody targeting CD40, was evaluated in this study for anti-tumor immunotherapy. The results demonstrated its manageable safety profile and pharmacokinetic/pharmacodynamic properties, suggesting its potential as a treatment option for solid malignancies.
INVESTIGATIONAL NEW DRUGS
(2023)
Article
Oncology
Victor Moreno, Juan Manuel Sepulveda, David A. Reardon, Angel Perez-Nunez, Pedro Gonzalez Leon, Bishoy Hanna, Ellen Filvaroff, Ida Aronchik, Henry Chang, Barbara Amoroso, Marlene Zuraek, Tania Sanchez-Perez, Cristina Mendez, Daniel Stephens, Zariana Nikolova, Michael A. Vogelbaum
Summary: This study investigates the pharmacokinetics, pharmacodynamics, and CNS penetration of the BET inhibitor trotabresib in patients with recurrent high-grade gliomas. The results show that trotabresib penetrates the blood-brain-tumor barrier and demonstrates target engagement in resected tumor tissue. The pharmacokinetics, pharmacodynamics, and safety of trotabresib in these patients are comparable to previous results in patients with advanced solid tumors.
Article
Oncology
Jayesh Desai, Peter Fong, Victor Moreno, Sophia Frentzas, Tarek Meniawy, Ben Markman, Mark Voskoboynik, Tahmina Rahman, Nageshwar Budha, John Wu, Jin Marlow, Silu Yang, Emiliano Calvo, Juan Martin-Liberal
Summary: This study investigated the safety and anti-tumor activity of BGB-A333, a PD-L1 inhibitor, alone and in combination with tislelizumab in patients with advanced solid tumors. The results showed that BGB-A333 in combination with tislelizumab demonstrated promising anti-tumor activity.
BRITISH JOURNAL OF CANCER
(2023)
Article
Cell Biology
Ignacio Melero, Tamara Tanos, Mariana Bustamante, Miguel F. Sanmamed, Emiliano Calvo, Irene Moreno, Victor Moreno, Tatiana Hernandez, Maria Martinez Garcia, Alejo Rodriguez-Vida, Josep Tabernero, Analia Azaro, Mariano Ponz-Sarvise, Iben Spanggaard, Kristoffer Rohrberg, Ernesto Guarin, Eveline Nuesch, Iakov I. Davydov, Chiahuey Ooi, Jose Duarte, Evelyne Chesne, Christine McIntyre, Maurizio Ceppi, Marta Canamero, Oliver Krieter
Summary: This first-in-human study evaluated the effectiveness of RO7122290, a bispecific fusion protein, in stimulating T cells for improved tumor cell killing in FAP-expressing tumors. The study involved administering escalating doses of RO7122290, both as a single agent and in combination with atezolizumab, to patients with advanced or metastatic solid tumors. The results showed promising pharmacokinetics and treatment-induced changes in peripheral and tissue biomarkers, supporting further evaluation of RO7122290 in combination with immune-oncology agents for solid tumor treatment.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Multidisciplinary Sciences
James J. Harding, Sarina A. Piha-Paul, Ronak H. H. Shah, Jessica J. Murphy, James M. Cleary, Geoffrey I. Shapiro, David I. Quinn, Irene Brana, Victor Moreno, Mitesh Borad, Sherene Loi, Iben Spanggaard, Haeseong Park, James M. Ford, Monica Arnedos, Salomon M. Stemmer, Christelle de la Fouchardiere, Christos Fountzilas, Jie Zhang, Daniel DiPrimeo, Casey Savin, S. Duygu Selcuklu, Michael F. Berger, Lisa D. Eli, Funda Meric-Bernstam, Komal Jhaveri, David B. Solit, Ghassan K. Abou-Alfa
Summary: In patients with biliary tract cancer, HER2 alterations correlate with poor prognosis. A phase II clinical trial showed that the tyrosine kinase inhibitor neratinib has some efficacy in treating advanced biliary tract cancers with HER2-mutation positive. The objective response rate to neratinib was 16% (95% CI 4.5-36.1%).
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Victor Moreno, Maria Vieito, Juan Manuel Sepulveda, Vladimir Galvao, Tatiana Hernandez-Guerrero, Bernard Doger, Omar Saavedra, Carmelo Carlo-Stella, Jean-Marie Michot, Antoine Italiano, Massimo Magagnoli, Cecilia Carpio, Antonio Pinto, Rafael Sarmiento, Barbara Amoroso, Ida Aronchik, Ellen Filvaroff, Bishoy Hanna, Xin Wei, Zariana Nikolova, Irene Brana
Summary: Bromodomain and extraterminal proteins (BET) are important in gene expression regulation and may play a role in cancer. In this study, the efficacy and safety of a BET inhibitor called trotabresib were evaluated in patients with advanced solid tumors and relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The results showed that trotabresib monotherapy had antitumor activity, with a response rate of 13.0% in DLBCL patients and a response rate of 0.0% in advanced solid tumor patients. These findings support further investigation of trotabresib in combination with other anticancer agents.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Lucia Paniagua-Herranz, Bernard Doger, Cristina Diaz-Tejeiro, Adrian Sanvicente, Cristina Nieto-Jimenez, Victor Moreno, Pedro Perez Segura, Balazs Gyorffy, Emiliano Calvo, Alberto Ocana
Summary: This study explored the high expression of EGFR and MET in prostate adenocarcinoma and pancreatic adenocarcinoma, and found that it was related to high expression of PD-L1, suggesting the potential for future combination therapy using bi-specific EGFR/MET antibodies and anti-PD(L)1 inhibitors.
Article
Oncology
Maria Vieito, Victor Moreno, Anna Spreafico, Irene Brana, Judy S. Wang, Meir Preis, Tatiana Hernandez, Sofia Genta, Aaron R. Hansen, Bernard Doger, Vladimir Galvao, Laurie Lenox, Regina J. Brown, Anna Kalota, Jaydeep Mehta, Friederike Pastore, Bharvin Patel, Pankaj Mistry, Junchen Gu, Josh Lauring, Manish R. Patel
Summary: In this study, a selective and potent PRMT5 inhibitor was evaluated for its safety and efficacy in advanced malignant solid tumors or non-Hodgkin lymphoma patients. The results showed that the inhibitor demonstrated good anti-tumor activity and manageable toxicity in treating adenoid cystic carcinoma and other tumor types. Two recommended doses were determined based on the study findings. The clinical benefits of the inhibitor in other tumor types were limited.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Funda Meric-Bernstam, Emiliano Calvo, Keun Seok Lee, Victor Moreno, Yeon Hee Park, Sun Young Rha, Pavani Chalasani, Wei Zhong, Li Zhou, Steven Pirie-Shepherd, Abraham C. F. Leung, Giuseppe Curigliano
Summary: This study evaluated the safety and antitumor activity of PF-06804103 in patients with advanced/unresectable or metastatic breast and gastric cancers. The results showed that PF-06804103 demonstrated antitumor activity, but adverse events led to a high rate of treatment discontinuation.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Oncology
Tatiana Hernandez Guerrero, Natalia Banos, Laura del Puerto Nevado, Ignacio Mahillo-Fernandez, Bernard Doger De-Speville, Emiliano Calvo, Michael Wick, Jesus Garcia-Foncillas, Victor Moreno
Summary: This study aimed to determine the factors that may predict better engraftment rates in patient-derived xenografts (PDXs). The use of systemic antibiotics and steroids by patients prior to sampling were found to impact the likelihood of success in PDX development. Furthermore, certain clinical, pathological, and molecular factors such as lactate dehydrogenase levels, grade of differentiation, Ki67 levels, presence of lymphovascular invasion, and mismatch repair status were correlated with engraftment success in PDXs.
Review
Pharmacology & Pharmacy
Tatiana Hernandez-Guerrero, Bernard Doger, Javier Luna, Ignacio Azinovich, Victor Moreno
Summary: This review discusses the use of nanoparticles as potential enhancers for the treatment of solid tumors, focusing specifically on hafnium oxide nanoparticles in clinical development in oncology.
DRUGS OF THE FUTURE
(2022)
Article
Oncology
Alexander Drilon, Daniel S. W. Tan, Ulrik N. Lassen, Serge Leyvraz, Yongmei Liu, Jyoti D. Patel, Lee Rosen, Benjamin Solomon, Ricarda Norenberg, Laura Dima, Nicoletta Brega, Lin Shen, Victor Moreno, Shivaani Kummar, Jessica J. Lin
Summary: The study assessed the efficacy and safety of larotrectinib in patients with TRK fusion-positive lung cancers. The results showed that larotrectinib had high activity, durable responses, extended survival benefit, and a favorable safety profile in advanced lung cancer patients with NTRK gene fusions, including those with CNS metastases.
JCO PRECISION ONCOLOGY
(2022)