Article
Chemistry, Medicinal
Fansheng Ran, Yun Liu, Zhongyuan Xu, Chi Meng, Dezhi Yang, Jianqiang Qian, Xuexian Deng, Yanan Zhang, Yong Ling
Summary: This review highlights the potential of BTK-based dual inhibitors in the treatment of various cancers and discusses the current status and future options in this field. It emphasizes the feasibility of these inhibitors for refractory tumors, including those with drug resistance.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Oncology
Jia Zhou, Yishi Li, Yangli Zhang, Haiyun Dai, Shuliang Guo
Summary: The T790M mutation is a major cause of drug resistance in lung cancer patients receiving EGFR-TKIs, with biomarkers such as brain metastases and longer initial treatment period of EGFR-TKIs linked to higher expression of T790M. Different rebiopsy methods may impact the progression time of patients.
Review
Chemistry, Multidisciplinary
Cindy Schelker, Patrycja Nowak-Sliwinska, Gerrit Borchard
Summary: Fixed-drug combinations have been used for cancer treatment, but current therapies have limitations in terms of resistance and toxicity. The combination of tyrosine kinase inhibitors and histone deacetylase inhibitors is being investigated in clinical trials and has shown promising results. Utilizing appropriate drug delivery systems, such as nanocarriers, can further enhance the activity and specificity of drug combinations. Strategies for the delivery of synergistic drug combinations for cancer treatment are discussed in this review.
JOURNAL OF CONTROLLED RELEASE
(2023)
Review
Oncology
Mariam Elshatlawy, Josephina Sampson, Katy Clarke, Richard Bayliss
Summary: Different variants of the EML4-ALK fusion gene in non-small cell lung cancer have different impacts on patient prognosis and metastatic risk. These variants form cellular compartments with distinct physical properties, which affect sensitivity to ALK tyrosine kinase inhibitors. The latest generation of ALK inhibitors is effective for most patients, but resistance can occur due to point mutations within the kinase domain of the EML4-ALK fusion.
MOLECULAR ONCOLOGY
(2023)
Review
Gastroenterology & Hepatology
Lorenza Rimassa, Richard S. Finn, Bruno Sangro
Summary: Single-agent immune checkpoint inhibitors (ICIs) have limited efficacy in advanced hepatocellular carcinoma (HCC) patients, and approximately 30% of patients show intrinsic resistance to ICIs. Therefore, researchers are exploring combination therapies, such as anti-angiogenic agents and other ICIs. Some trials have shown promising results and potential for clinical application. However, there are still many unanswered questions that require further research.
JOURNAL OF HEPATOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ying Xie, Sen-ling Feng, Fang He, Pei-Yu Yan, Xiao-Jun Yao, Xing-Xing Fan, Elaine Lai-Han Leung, Hua Zhou
Summary: This study investigates the potential of targeting the Nrf2 pathway to overcome acquired drug resistance and enhance the therapeutic effects of chemotherapy and molecular-targeted therapy. It demonstrates that upregulation of Nrf2 in Gefitinib-resistant and paclitaxel-resistant lung cancer cells is an important mechanism.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Cell Biology
Laura Pacini, Andrew D. Jenks, Nadia Carvalho Lima, Paul H. Huang
Summary: Lung cancer is the most common cause of cancer-related deaths globally, and genetic alterations in the FGFR family in non-small cell lung cancer play a role in cancer initiation and progression. Therapies targeting FGFR have been developed, but clinical trials have shown low efficacy in lung cancer patients with FGFR aberrations.
Article
Oncology
Ze Zhang, Tianyu Jiao, Junfeng Li, Bingyang Hu, Wenwen Zhang, Zhijun Wang, Tao Wan, Yafei Wang, Shichun Lu
Summary: This study aimed to explore the potential efficacy of treatment based on TKIs in combination with PD-1 inhibitors for unresectable recurrent HCC. The results showed that the combination therapy of TKIs and PD-1 inhibitors can significantly prolong the survival of patients.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2023)
Article
Pharmacology & Pharmacy
Elisa Herraez, Ruba Al-Abdulla, Meraris Soto, Oscar Briz, Dominik Bettinger, Heike Bantel, Sofia del Carmen, Maria A. Serrano, Andreas Geier, Jose J. G. Marin, Rocio I. R. Macias
Summary: Impaired function of organic cation transporter 1 (OCT1) in hepatocellular carcinoma (HCC) has been associated with unsatisfactory response to sorafenib. However, some patients lacking OCT1 at the plasma membrane (PM) of HCC cells still respond to sorafenib, suggesting that another transporter may contribute to take up this drug. The aim of this study was to investigate whether OCT3 could contribute to the uptake of sorafenib and other tyrosine kinase inhibitors (TKIs) and whether OCT3 determination can predict HCC response to sorafenib. Functional in vitro studies revealed that OCT3 is also able to mediate sorafenib uptake. Other TKIs, such as regorafenib, lenvatinib, and cabozantinib can also interact with this transporter. In HCC samples, OCT3 was expressed at the PM of cancer cells, and its presence, detected in 26% of tumors, was associated with better outcomes in patients treated with sorafenib. Analysis by immunohistochemistry of OCT3 in the PM of tumor cells may help to predict the response of HCC patients to sorafenib and potentially to other TKIs.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Giulia Romano, Patricia Le, Giovanni Nigita, Michela Saviana, Lavender Micalo, Francesca Lovat, Daniel del Valle Morales, Howard Li, Patrick Nana-Sinkam, Mario Acunzo
Summary: Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation show a positive initial response to tyrosine kinase inhibitors (TKIs), but rapid resistance is often developed due to genetic alterations, including amplification of hepatocyte growth factor receptor (MET) and its abnormal activity. The role of RNA post-transcriptional modifications, specifically adenosine-to-inosine (A-to-I) RNA editing, in the aberrant expression of MET in cancer, particularly NSCLC, is not well-studied. In this study, the researchers investigated the effect of edited miR-411-5p on NSCLC cell lines and found that it directly targets MET and negatively affects the mitogen-activated protein kinases (MAPKs) pathway. By overexpressing edited miR-411-5p, the researchers observed reduced proliferation and increased apoptosis in TKI-resistant NSCLC cells, indicating a potential improvement in EGFR TKI response.
Article
Biochemistry & Molecular Biology
Robert Walmsley, Derek S. Steele, Georgina M. Ellison-Hughes, Sotiris Papaspyros, Andrew J. Smith
Summary: This study investigated the effects of imatinib, a receptor tyrosine kinase inhibitor, on human cardiac progenitor cells. It was found that imatinib reduced cell viability, depolarized mitochondria, increased lysosome and autophagosome content, and induced cell death through necroptosis. However, the toxicity could be rescued by RIP1 inhibition and autophagy played a partial role in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Manali Tilak, Jennifer Holborn, Laura A. New, Jasmin Lalonde, Nina Jones
Summary: Glioblastoma multiforme (GBM) is a deadly cancer with limited response to existing therapies. Subtypes of GBM with distinct genetic signatures show aberrant activation of signal transduction pathways. Current research focuses on understanding these molecular alterations to develop more efficient targeted therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Florent Puisset, Mourad Mseddi, Loic Mourey, Damien Pouessel, Benoit Blanchet, Etienne Chatelut, Christine Chevreau
Summary: This article discusses the rationale, benefits, and limits of therapeutic drug monitoring for the seven tyrosine kinase inhibitor compounds used to treat advanced renal cell carcinoma. These seven compounds with anti-angiogenic properties remain key drugs for treating advanced renal cell carcinoma. There is a strong rationale for implementing therapeutic drug monitoring for these drugs, and general considerations for monitoring anticancer drugs are presented, with a focus on oral therapy. The pharmacokinetics, factors of inter- and intraindividual variabilities, and pharmacokinetic/pharmacodynamic relationships of these tyrosine kinase inhibitors are described. The benefits and limits of therapeutic drug monitoring as a routine practice are also discussed.
Article
Cell Biology
Hassan Reda Hassan Elsayed, Randa El-Gamal, Mohammed R. Rabei, Mona G. Elhadidy, Shereen Hamed, Basma H. Othman, Mohamed Mahmoud Abdelraheem Elshaer, Mostafa Khaled Sedky, Ahmed Tarek Abd Elbaset Hassan, Mohammad El-Nablaway
Summary: This study suggests that Dasatinib may improve renal function by correcting renal changes caused by obesity. The results show that Dasatinib can attenuate renal inflammation and fibrosis, enhance renal autophagy, and thereby benefit obesity-related renal issues.
Review
Oncology
Weina Guo, Keye Du, Shanshan Luo, Desheng Hu
Summary: Lung cancer is the most common oncological disease worldwide, with non-small cell lung cancer being the majority. Significant advancements in the treatment of non-small cell lung cancer have improved our understanding of tumor biology and progression mechanisms. Autophagy plays an important role in the progression of non-small cell lung cancer and resistance to treatment, making it a potential therapeutic target.
FRONTIERS IN ONCOLOGY
(2022)
Review
Engineering, Biomedical
Sanja Aveic, Rogerio B. Craveiro, Michael Wolf, Horst Fischer
Summary: Clinical evidence suggests that continuous remodeling of tooth root cementum and periodontal apparatus is crucial in maintaining tissue strength and securing teeth anchorage. The interaction between tooth root cementum and periodontal ligament plays a key role in tissue homeostasis. Various in vitro models and biomaterials have been utilized to study the physiological and pathophysiological conditions of periodontal tissues, with the aim of advancing regenerative strategies.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Oncology
Stefania D'Agostino, Lucia Tombolan, Mattia Saggioro, Chiara Frasson, Elena Rampazzo, Stefania Pellegrini, Francesca Favaretto, Carlo Biz, Pietro Ruggieri, Piergiorgio Gamba, Paolo Bonvini, Sanja Aveic, Roberto Giovannoni, Michela Pozzobon
Summary: The study demonstrates that unlike epithelial cancers, rhabdomyosarcoma (RMS) cells play a direct role in remodeling their own ECM and are less dependent on support from cancer-associated fibroblasts (CAFs). In both 2D and 3D models, the rate of interaction between RMS cells and fibroblasts is significantly lower, indicating a reduced reliance on CAFs for tumor growth.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Vito Alessandro Lasorsa, Annalaura Montella, Sueva Cantalupo, Matilde Tirelli, Carmen de Torres, Sanja Aveic, Gian Paolo Tonini, Achille Iolascon, Mario Capasso
Summary: This study focuses on noncoding cis-regulatory variants in neuroblastoma and identifies somatic mutations in regulatory elements that play a role in tumorigenesis. The findings highlight the importance of assessing these variants and long-range interactions in understanding the drivers of neuroblastoma.
Article
Materials Science, Biomaterials
Mattia Saggioro, Stefania D'Agostino, Anna Gallo, Sara Crotti, Sara D'Aronco, Diana Corallo, Giulia Veltri, Gabriele Martinez, Antonella Grigoletto, Anna Maria Tolomeo, Giovanni Tafuro, Marco Agostini, Sanja Aveic, Valentina Serafin, Alessandra Semenzato, Gianfranco Pasut, Michela Pozzobon
Summary: Hydrogels offer important advantages for 3D cell culture, and a biocompatible hyaluronic acid-polyethylene glycol hydrogel was developed to study the migratory behavior of alveolar rhabdomyosarcoma cells. Proteomic analysis revealed the composition of the extracellular matrix, and the optimal hydrogel for ARMS cell growth was selected based on various factors. The study validated the role of the fibronectin receptor ITGA5 in ARMS cell migration and investigated key pathways using a reverse phase protein array to understand potential hallmarks of cancer cell resistance and dissemination.
BIOMATERIALS SCIENCE
(2021)
Article
Cell Biology
Diana Corallo, Carlo Zanon, Marcella Pantile, Gian Paolo Tonini, Angelica Zin, Samuela Francescato, Bartolomeo Rossi, Eva Trevisson, Claudia Pinato, Ezequiel Monferrer, Rosa Noguera, Salvador F. Alino, Maria Jose Herrero, Alessandra Biffi, Elisabetta Viscardi, Sanja Aveic
Summary: The genetic landscape of an aggressive NB has been depicted through comprehensive analysis, combining CNAs, SNVs, and SNPs analyses along with characterization of 3D tumoroids. The integrated approach proved powerful in evaluating clonal evolution and dynamic genomic alterations during disease progression and therapy administration, enhancing disease follow-up and tumor recurrence prediction.
Article
Chemistry, Medicinal
Romeo Romagnoli, Paola Oliva, Filippo Prencipe, Stefano Manfredini, Federico Ricci, Diana Corallo, Sanja Aveic, Elena Mariotto, Giampietro Viola, Roberta Bortolozzi, Maria Paola Germano, Laura De Luca
Summary: A series of cinnamide compounds linked with 1-aryl piperazines, derived from cinnamic acid derivatives, were synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. The presence of a 3-chloro-4-fluorophenyl moiety at the N-1 position of the piperazine ring was found to be essential for a potent inhibitory effect. Molecular docking studies were conducted to investigate the interactions between the compounds and the active site of the enzyme. Some of the highly active compounds also showed potential in inhibiting melanogenesis. However, certain compounds exhibited toxicity at high concentrations.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Paola Oliva, Romeo Romagnoli, Barbara Cacciari, Stefano Manfredini, Chiara Padroni, Andrea Brancale, Salvatore Ferla, Ernest Hamel, Diana Corallo, Sanja Aveic, Noemi Milan, Elena Mariotto, Giampietro Viola, Roberta Bortolozzi
Summary: In this study, two series of compounds were found to exhibit moderate to potent antiproliferative activity against cancer cells. The interaction with tubulin led to cell apoptosis and inhibition of cell growth.
Article
Chemistry, Medicinal
Romeo Romagnoli, Paola Oliva, Filippo Prencipe, Stefano Manfredini, Federica Budassi, Andrea Brancale, Salvatore Ferla, Ernest Hamel, Diana Corallo, Sanja Aveic, Lorenzo Manfreda, Elena Mariotto, Roberta Bortolozzi, Giampietro Viola
Summary: A study was conducted to synthesize a series of new compounds with potential antitumor activity. Among these compounds, three showed significantly higher activity compared to others. These compounds demonstrated strong antiproliferative effects on different cancer cell lines and were able to induce apoptosis through various mechanisms. In vivo experiments using a zebrafish model also showed promising results in reducing tumor mass.
Article
Materials Science, Biomaterials
Ramin Nasehi, Jana Schieren, Caroline Grannemann, Alena L. Palkowitz, Aaron Babendreyer, Nicole Schwarz, Sanja Aveic, Andreas Ludwig, Rudolf E. Leube, Horst Fischer
Summary: The modality of hydrostatic pressure during nozzle-based bioprinting affects the biological response of processed cells differently. Pulsatile hydrostatic pressure leads to an immediate increase of intracellular ATP in both endothelial and epithelial cells. Bioprinting-associated hydrostatic pressure triggers a pro-inflammatory response in endothelial cells but not in epithelial cells.
BIOMATERIALS ADVANCES
(2023)
Article
Engineering, Biomedical
Ramin Nasehi, Ali T. Abdallah, Marcella Pantile, Carlo Zanon, Michael Vogt, Stephan Ruetten, Horst Fischer, Sanja Aveic
Summary: The lack of in vitro cell models is a challenge for discovering new molecular targets and therapeutics for pediatric bone metastatic disease. Using a beta-tricalcium phosphate (β-TCP) multicellular 3D in vitro bone microtissue model, the study successfully reconstitutes key phenotypic and transcriptional patterns of native metastatic tumor cells and enhances their stemness and proinvasive features. The geometry and chemical impact of β-TCP reveals a prometastatic landscape of the tumor microenvironment, providing insights for further analysis of the disease and preclinical target validations.
MATERIALS TODAY BIO
(2023)
Article
Pharmacology & Pharmacy
Diana Corallo, Marco Dalla Vecchia, Daria Lazic, Sabine Taschner-Mandl, Alessandra Biffi, Sanja Aveic
Summary: Cell motility is a crucial process in multicellular organisms and is essential for tissue formation and regeneration, but uncontrolled cell motility can lead to various diseases including neoplasms. This review focuses on the regulatory mechanisms of metastatic neuroblastoma, a solid pediatric tumor originating from migratory cells in the neural crest. Targeting intracellular and extracellular processes involved in the highly motile phenotype of metastatic neuroblastoma cells could improve treatment for high-risk patients. The development of migration-inhibiting compounds and standardized preclinical approaches for selecting anti-metastatic drugs in neuroblastoma is also discussed.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maike Sahle, Mattis Wachendoerfer, Alena L. Palkowitz, Ramin Nasehi, Sanja Aveic, Horst Fischer
Summary: Fibrin-based hydrogel blends can increase the long-term stability of in vitro gingival models, mimicking the histology of native gingiva and providing a new perspective for evaluating specific biological or pathological conditions of artificial gingival tissue.
MACROMOLECULAR BIOSCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Ghazi Ben Messaoud, Sanja Aveic, Mattis Wachendoerfer, Horst Fischer, Walter Richtering
Summary: Porous hydrogels derived from aqueous two-phase systems (ATPS) are an interesting alternative to overcome the restricted porosity of most hydrogels in vitro. By tuning the phase behavior and concentration, ATPS hydrogels with three distinct microstructures, including bicontinuous hydrogels with interconnected pores, can be formed. These ATPS hydrogels show cytocompatibility and can sustain their unique porous structure when processed by inkjet and microextrusion techniques.
Meeting Abstract
Cell & Tissue Engineering
Sanja Aveic, Max Seidelmann, Simon Janssen, Ramin Nasehi, Horst Fischer
TISSUE ENGINEERING PART A
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Vito Alessandro Lasorsa, Sueva Cantalupo, Carmen De Torres, Sanja Aveic, Gian Paolo Tonini, Achille Iolascon, Mario Capasso
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
