Article
Oncology
Ilias Tsochantaridis, Georgia-Persephoni Voulgaridou, Alexandra Giatromanolaki, Michael I. Koukourakis, Mihalis I. Panayiotidis, Aglaia Pappa
Summary: Specific ALDH isoforms are important mediators for the acquisition of a CSC phenotype in non-small cell lung and hepatocellular carcinomas, suggesting their potential as promising targets for therapeutic approaches.
ANTICANCER RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Naoya Hirata, Shigeru Yamada, Shota Yanagida, Atsushi Ono, Yasunari Kanda
Summary: Current research suggests that FTY720 is effective in inhibiting breast cancer stem cells in vitro, potentially reducing the expression of stem cell markers through upregulation of protein phosphatase 2A (PP2A).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Dejian Li, Kai Zhao, Ziwen Zhao, Bo Jiang, Xianxu Gong, Yan Zhang, Yingqi Guo, Han Xiao, Ye Wang, Hui Liu, Chengqing Yi, Wenguang Gu
Summary: The study identified dysregulation of miRNAs in MFH, with 16 upregulated and 31 downregulated. Differential miRNAs showed different expression in cell resistant strains compared to the control group. Quantitative polymerase chain reaction confirmed significant variations in seven miRNAs and four target genes. Hsa-miR-206 was found to significantly inhibit MFH proliferative activity.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Nicola Cirillo, Carmen Wu, Stephen S. Prime
Summary: The discovery of cancer stem cells has changed our understanding of cancer biology, with specific subsets of head and neck cancer stem cells playing different roles in tumor development and resistance to treatment.
Article
Medicine, Research & Experimental
Gozde Kayadibi Koygun, Meltem Demirel Kars, Ayca Emsen, Hasibe Artac, Faruk Aksoy, Murat Cakir, Lema Tavli, Mehmet Artac
Summary: This study aimed to evaluate the response of breast cancer stem-like cells (BCSCs) to trastuzumab, finding that HER2(+) BCSCs were more sensitive to the drug compared to HER2(-) BCSCs. MMPs and cytokines were expressed at higher levels in HER2(+) BCSCs, suggesting potential metastatic capacity. Further research on MMPs is needed for targeted drug therapy of BCSCs.
CLINICAL AND EXPERIMENTAL MEDICINE
(2021)
Review
Oncology
Pavan Kumar Dhanyamraju, Todd D. Schell, Shantu Amin, Gavin P. Robertson
Summary: One of the challenges in cancer treatment is the development of acquired resistance to therapy, which is responsible for a large percentage of cancer-related deaths. This review focuses on persister cells, a subpopulation of drug-tolerant cells in tumors, and discusses approaches to target them. The review highlights the characteristics of a specific persister cell subpopulation with high levels of aldehyde dehydrogenase (ALDH) activity and their role in drug resistance and cancer progression. The interactions between ALDH-high persister cells and the tumor microenvironment are also explored. Therapeutic modulation of this subpopulation is proposed as a strategy for more effective cancer management.
Article
Oncology
Yu-Hsun Chang, Kun-Chi Wu, Dah-Ching Ding
Summary: The study found that n-butylidenephthalide (BP) can kill cancer stem cells (CSCs) of high-grade serous ovarian cancer (HGSOC) by inducing apoptosis, providing a new therapeutic approach for treating HGSOC.
Article
Biochemistry & Molecular Biology
Martha B. Alvarez-Elizondo, Daphne Weihs
Summary: In this study, the invasiveness of CD44(+)ALDH(+) cancer stem-like cells (CSCs) was investigated using a rapid mechanobiology-based assay. It was found that CD44(+)ALDH(+) cells showed higher invasiveness and migratory capacity, suggesting their potential role in disease progression and as prognostic markers for recurrence and metastasis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Medicine, Research & Experimental
Shruthi Sriramkumar, Riddhi Sood, Thomas D. Huntington, Ahmed H. Ghobashi, Truc T. Vuong, Tara X. Metcalfe, Weini Wang, Kenneth P. Nephew, Heather M. O'Hagan
Summary: This study reveals the impact of platinum-based chemotherapy on metabolic pathways and identifies key targets that can be therapeutically exploited to inhibit platinum-induced enrichment of OCSCs, ultimately improving the survival of OC patients.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Lucia Benitez, Lucas Barberis, Luciano Vellon, Carlos A. Condat
Summary: Cancer stem cells play a crucial role in the development of solid tumors, receiving signals from their environment that affect cell dynamics. A mathematical model was used to analyze experiments in China, showing that interactions between cancer stem cells and differentiated cancer cells can determine growth dynamics. Stiffer substrates lead to more asymmetric stem cell divisions, influencing the growth of cancer stem cell populations.
Article
Chemistry, Multidisciplinary
Miae Won, Ji Hyeon Kim, Myung Sun Ji, Jong Seung Kim
Summary: ALDH, a cancer stem cell biomarker associated with drug resistance, can be targeted using a prodrug called DE-CPT, which efficiently decreases the population of CSCs and kills cancer cells.
CHEMICAL COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
John Verigos, Dimitris Kordias, Styliani Papadaki, Angeliki Magklara
Summary: Cancer stem cells play a significant role in chemoresistance, tumor recurrence, and metastasis in breast cancer, making them a promising target for new therapies. Through RNA-sequencing, researchers identified differential gene expression patterns between breast CSCs and non-CSCs, with the TRPM4 gene being found to be overexpressed in tumorspheres and affecting stemness properties. Inhibiting TRPM4 showed potential anti-tumor effects by targeting the bCSC subpopulation, suggesting a novel therapeutic approach for improving breast cancer treatments.
Article
Biochemistry & Molecular Biology
Sahily Rodriguez Torres, Loraine Gresseau, Meriem Benhamida, Yuniel Fernandez-Marrero, Borhane Annabi
Summary: Three-dimensional tumorsphere cultures are useful in vitro models to investigate the effects of drugs on cancer stem cells. Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea leaves, can inhibit ovarian cancer cell proliferation. However, its ability to suppress cancer stemness traits in ovarian malignancies needs further exploration.
Article
Oncology
Yunhee Lee, Junghwa Yoon, Dongjoon Ko, Minyeong Yu, Soojin Lee, Semi Kim
Summary: TMPRSS4 promotes cancer stem cell features in prostate cancer by upregulating the stem cell factor SOX2 through the EMT-inducing transcription factors SLUG and TWIST1. This novel mechanism may play a crucial role in tumor progression control.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Karina Lindbog Madsen, Niels Langkjaer, Oke Gerke, Poul F. Hoilund-Carlsen, Birgitte Brinkmann Olsen
Summary: The high recurrence rate of lung cancer is a major challenge in clinical practice, which is associated with therapy-resistant cancer stem cells (CSCs). This study aimed to evaluate the effects of Auger electrons on patient-derived lung cancer tumorspheres enriched in CSCs. The results showed that Auger electrons induced DNA double-strand breaks, cell cycle arrest, and apoptosis in tumorspheres, but the sensitivity to Auger electron irradiation varied among tumorspheres derived from different patients.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2022)
Article
Cell Biology
Karmele Valencia, Cristina Sainz, Cristina Bertolo, Gabriel de Biurrun, Jackeline Agorreta, Arantza Azpilikueta, Marta Larrayoz, Graziella Bosco, Carolina Zandueta, Miriam Redrado, Esther Redin, Francisco Exposito, Diego Serrano, Mirari Echepare, Daniel Ajona, Ignacio Melero, Ruben Pio, Roman Thomas, Alfonso Calvo, Luis M. Montuenga
Summary: There is a lack of adequate mouse models and cell lines for studying lung squamous cell carcinoma (LUSC). In this study, two models of transplantable LUSC cell lines were generated and characterized, revealing similar genetic and transcriptomic patterns. The immune landscape and response to immune checkpoint inhibition were also compared. Furthermore, the metastatic potential of these models showed organotropism similar to LUSC in humans. Overall, these valuable cell line tools recapitulate the complexity of the human disease.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Catia Monteiro, Lauritz Miarka, Maria Perea-Garcia, Neibla Priego, Pedro Garcia-Gomez, Laura Alvaro-Espinosa, Ana de Pablos-Aragoneses, Natalia Yebra, Diana Retana, Patricia Baena, Coral Fustero-Torre, Osvaldo Grana-Castro, Kevin Troule, Eduardo Caleiras, Patricia Tezanos, Pablo Muela, Elisa Cintado, Jose Luis Trejo, Juan Manuel Sepulveda, Pedro Gonzalez-Leon, Luis Jimenez-Roldan, Luis Miguel Moreno, Olga Esteban, Angel Perez-Nunez, Aurelio Hernandez-Lain, Jose Mazarico Gallego, Irene Ferrer, Rocio Suarez, Eva M. Garrido-Martin, Luis Paz-Ares, Celine Dalmasso, Elizabeth Cohen-Jonathan Moyal, Aurore Siegfried, Aisling Hegarty, Stephen Keelan, Damir Vareslija, Leonie S. Young, Malte Mohme, Yvonne Goy, Harriet Wikman, Jose Fernandez-Alen, Guillermo Blasco, Lucia Alcazar, Clara Cabanuz, Sergei Grivennikov, Andrada Ianus, Noam Shemesh, Claudia C. Faria, Rebecca Lee, Paul Lorigan, Emilie Le Rhun, Michael Weller, Riccardo Soffietti, Luca Bertero, Umberto Ricardi, Joaquim Bosch-Barrera, Elia Sais, Eduard Teixidor, Alejandro Hernandez-Martinez, Alfonso Calvo, Javier Aristu, Santiago M. Martin, Alvaro Gonzalez, Omer Adler, Neta Erez, Manuel Valiente
Summary: This study identifies a molecular mechanism underlying resistance to whole-brain radiotherapy and suggests potential targets and biomarkers for personalized radiotherapy. The findings have important implications for improving the efficacy of treatment for patients with brain metastasis.
Article
Medicine, Research & Experimental
Virginia Laspidea, Montserrat Puigdelloses, Sara Labiano, Lucia Marrodan, Marc Garcia-Moure, Marta Zalacain, Marisol Gonzalez-Huarriz, Naiara Martinez-Velez, Iker Ausejo-Mauleon, Daniel de la Nava, Guillermo Herrador-Canete, Javier Marco-Sanz, Elisabeth Guruceaga, Carlos E. de Andrea, Maria Villalba, Oren Becher, Massimo Squatrito, Veronica Matia, Jaime Gallego Perez-Larraya, Ana Patino-Garcia, Sumit Gupta, Candelaria Gomez-Manzano, Juan Fueyo, Marta M. Alonso
Summary: The study found that Delta-24-ACT treatment with oncolytic adenovirus can significantly improve the survival rate of mice with DIPG, leading to long-term survival and the development of immunological memory. In addition, this treatment method is safe and has no toxic side effects, and can modulate tumor-immune content.
Review
Oncology
Irati Garmendia, Esther Redin, Luis M. Montuenga, Alfonso Calvo
Summary: YES1, a nonreceptor tyrosine kinase, is considered as an emerging target in solid tumors. It is overexpressed in many tumor types, promoting cell proliferation and invasiveness. Novel specific inhibitors of YES1 have shown impressive antitumor effects in pre-clinical models. Inhibiting YES1 in tumors with high expression of this protein is a promising strategy against cancer.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Medicine, General & Internal
Jaime Gallego Perez-Larraya, Marc Garcia-Moure, Sara Labiano, Ana Patino-Garcia, Jessica Dobbs, Marisol Gonzalez-Huarriz, Marta Zalacain, Lucia Marrodan, Naiara Martinez-Velez, Montserrat Puigdelloses, Virginia Laspidea, Itziar Astigarraga, Blanca Lopez-Ibor, Ofelia Cruz, Miren Oscoz Lizarbe, Sandra Hervas-Stubbs, Gorka Alkorta-Aranburu, Ibon Tamayo, Beatriz Tavira, Ruben Hernandez-Alcoceba, Chris Jones, Gitanjali Dharmadhikari, Cristian Ruiz-Moreno, Henk Stunnenberg, Esther Hulleman, Jasper van der Lugt, Miguel A. Idoate, Ricardo Diez-Valle, Ines Esparragosa Vazquez, Maria Villalba, Carlos de Andrea, Jorge M. Nunez-Cordoba, Brett Ewald, Joan Robbins, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F. Lang, Sonia Tejada, Marta M. Alonso
Summary: This study investigated the use of oncolytic virus DNX-2401 in pediatric patients with diffuse intrinsic pontine glioma (DIPG). The results showed that treatment with DNX-2401 led to changes in T-cell activity and reduction or stabilization of tumor size in some patients, but also caused adverse events.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Fernando Torres Andon, Sergio Leon, Aldo Ummarino, Esther Redin, Paola Allavena, Diego Serrano, Clement Anfray, Alfonso Calvo
Summary: TLRs serve as natural initial triggers of immune responses and hold potential in cancer immunotherapy. Intratumoral injection of TLR agonists achieves high local drug exposure and strong antitumor response, potentially leading to cure and antitumor immunological memory.
Article
Clinical Neurology
Seojin Lee, Ivan Martinez-Valbuena, Carlos E. de Andrea, Maria Villalba-Esparza, Suganthini Ilaalagan, Blas Couto, Naomi P. Visanji, Anthony E. Lang, Gabor G. Kovacs
Summary: This study provides the first cell type-specific evaluation of iron homeostasis and oxygen homeostasis in relation to tau pathology in patients with progressive supranuclear palsy (PSP). Astrocytes were identified as the major cell type accumulating iron in the early affected regions of PSP, highly associated with tau pathology. Dysregulated expression of iron and oxygen homeostasis genes associated with brain aging was also found, as well as dysregulated expression of rare neurodegeneration with brain iron accumulation (NBIA) genes associated with tau pathology, distinguishing PSP from the healthy aging brain.
ANNALS OF NEUROLOGY
(2023)
Article
Immunology
Karmele Valencia, Mirari Echepare, Alvaro Teijeira, Andrea Pasquier, Cristina Bertolo, Cristina Sainz, Ibon Tamayo, Benat Picabea, Graziella Bosco, Roman Thomas, Jackeline Agorreta, Jose Maria Lopez-Picazo, Joan Frigola, Ramon Amat, Alfonso Calvo, Enriqueta Felip, Ignacio Melero, Luis M. Montuenga
Summary: Valencia et al. have identified DSTYK as a novel therapeutic target in lung cancer. Inhibition of DSTYK sensitizes lung cancer cells to T cell-mediated killing and impairs mitochondrial fitness and cytoprotective autophagy. DSTYK copy number gain predicts lack of response to immunotherapy in lung cancer patients.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Medicine, Research & Experimental
Amy R. Cross, Carlos E. de Andrea, Maria Villalba-Esparza, Manuel F. Landecho, Lucia Cerundolo, Praveen Weeratunga, Rachel E. Etherington, Laura Denney, Graham Ogg, Ling -Pei Ho, Ian S. D. Roberts, Joanna Hester, Paul Klenerman, Ignacio Melero, Stephen N. Sansom, Fadi Issa
Summary: This study used spatial transcriptomics to explore the interactions between different immune and stromal cell populations in COVID-19-affected lung tissue. Through gene expression analysis of well-preserved lung samples from 3 patients, a common immune-cell signaling circuit involving cytotoxic lymphocytes and pro-inflammatory macrophages was identified in areas of severe lung damage. The expression of IFNG by cytotoxic lymphocytes was associated with the induction of chemokines, while TNF superfamily members (BAFF and TRAIL) were consistently upregulated in severely damaged areas. Validation of these findings in additional COVID-19 patient cohorts supports the potential use of this immune-mediated tissue pathology model for future therapeutic strategies.
Article
Oncology
Francisco Exposito, Miriam Redrado, Maeva Houry, Katherine Hastings, Magdalena Molero-Abraham, Teresa Lozano, Jose Luis Solorzano, Julian Sanz-Ortega, Vera Adradas, Ramon Amat, Esther Redin, Sergio Leon, Naroa Legarra, Javier Garcia, Diego Serrano, Karmele Valencia, Camila Robles-Oteiza, Giorgia Foggetti, Nerea Otegui, Enriqueta Felip, Juan J. Lasarte, Luis Paz-Ares, Jon Zugazagoitia, Katerina Politi, Luis Montuenga, Alfonso Calvo
Summary: Immunotherapy resistance in non-small cell lung cancer (NSCLC) can be attributed to an immunosuppressive microenvironment created by genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression. PTEN-low tumors are associated with higher levels of immune checkpoint proteins and poorer response to immunotherapy. Preclinical models demonstrate that PTEN loss promotes metastasis and fibrosis, and facilitates the conversion of immune cells into immunosuppressive regulatory T cells (Treg). However, targeting PTEN loss-mediated immunosuppression can reverse immunotherapy resistance in NSCLC.
Review
Oncology
Nerea Otegui, Maeva Houry, Imanol Arozarena, Diego Serrano, Esther Redin, Francisco Exposito, Sergio Leon, Karmele Valencia, Luis Montuenga, Alfonso Calvo
Summary: Immunotherapy for NSCLC is effective for some patients, but less than half of them will benefit from it. Detection of PD-L1 in tumors is currently the only validated predictive biomarker. Genetic and metabolic alterations in tumor cells can affect the tumor microenvironment and the response to immunotherapy. Novel strategies based on these alterations may improve the efficacy of immunotherapy for lung cancer patients.
Editorial Material
Oncology
Karmele Valencia, Luis M. Montuenga, Alfonso Calvo
Summary: The influence of sex on immunotherapy response in patients with non-small cell lung cancer (NSCLC) is inconclusive. However, a recent study suggests that the existence of a 17 beta-estradiol/ER alpha/PDL1 signaling loop in NSCLC is a key factor determining the response to immunotherapy, opening up new therapeutic options.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Paola Anna Jablonska, Nuria Galan, Jennifer Barranco, Sergio Leon, Ramon Robledano, Jose Ignacio Echeveste, Alfonso Calvo, Javier Aristu, Diego Serrano
Summary: This study investigates the role of STAT3 and other inflammatory markers in the development of brain radiation necrosis (RN). The results suggest that STAT3 plays an important role in RN development, and targeting STAT3 may be a promising strategy for ameliorating symptomatic RN in brain metastases patients undergoing stereotactic radiosurgery (SRS).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.