Article
Surgery
Krishna Modi, Maria Segovia, Alisha Mavis, Thomas Schiano, Yuval Patel, Justin Boike, Debra Sudan, Shunji Nagai, Syed-Mohammed Jafri
Summary: This descriptive study reviewed the outcomes of mTOR inhibitors in intestinal and multivisceral transplantation, finding potential renal safety profile in some patients, but limited use due to side effects tolerance.
CLINICAL TRANSPLANTATION
(2021)
Article
Oncology
Robin K. Kelley, Nancy M. Joseph, Halla S. Nimeiri, Jimmy Hwang, Laura M. Kulik, Zoe Ngo, Spencer C. Behr, Courtney Onodera, Karen Zhang, Andrea G. Bocobo, Al B. Benson, Alan P. Venook, John D. Gordan
Summary: In this phase II study, the combination of temsirolimus and sorafenib demonstrated acceptable safety but did not achieve the target threshold for efficacy in hepatocellular carcinoma patients. Tumor next-generation sequencing showed mTOR pathway mutations in some patients, but these mutations were not directly associated with treatment response.
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)
Review
Neurosciences
Henry Querfurth, Han-Kyu Lee
Summary: mTOR is involved in regulating energy metabolism, neuronal growth, insulin signaling, and autophagy, playing both beneficial and pathogenic roles in neurodegenerative diseases. Balanced actions of mTOR complexes may have implications for Alzheimer's disease, Parkinson's disease, Huntington's disease, Frontotemporal dementia, and Amyotrophic Lateral Sclerosis. Beyond rapamycin, rapalogs with improved tolerability and delivery modes hold promise in treating age-related conditions.
MOLECULAR NEURODEGENERATION
(2021)
Article
Cell Biology
You-Liang Lai, Kai-Hung Wang, Hsing-Pang Hsieh, Wan-Ching Yen
Summary: DBPR114 showed activity against HCC tumor cell proliferation in vitro regardless of p53 alteration status and tumor grade. It induced growth inhibition in HCC cells through apoptosis induction, cell cycle arrest, and polyploidy formation. DBPR114 also exhibited anti-angiogenic effects and significantly inhibited tumor growth in multiple HCC tumor xenograft models.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
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
Medicine, Research & Experimental
Shuhua Wei, Fenghua Wei, Mengyuan Li, Yuhan Yang, Jingwen Zhang, Chunxiao Li, Junjie Wang
Summary: Sorafenib, a multi-kinase inhibitor, has been approved for cancer treatment, especially hepatocellular carcinoma (HCC). However, many cancer patients acquire drug resistance to sorafenib in subsequent treatment, and the immunological mechanisms behind this resistance are still unclear. This review focuses on the immunoregulatory effects of sorafenib on the tumor microenvironment, the potential immunological mechanisms of therapeutic resistance, and the combination of sorafenib with immunotherapy to improve efficacy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Dermatology
Shenyu Zhu, Wenbo Yu, Jianfeng Gao, Jianxian Xiong
Summary: A meta-analysis showed that heart transplant recipients on mammalian target of rapamycin inhibitors (MTRIs) had a significantly higher frequency of wound complications (WCs) compared to those on control.
INTERNATIONAL WOUND JOURNAL
(2023)
Article
Medicine, Research & Experimental
Mohamed El-Tanani, Hamdi Nsairat, Alaa A. Aljabali, Angel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Gowhar A. Naikoo, Walhan Alshaer, Murtaza M. Tambuwala
Summary: The mammalian target of rapamycin (mTOR), a signalling system, is necessary for various cell proliferation activities. It recognizes PI3KAKT stress signals as a serine-threonine kinase. The abnormal regulation of mTOR pathway has been proven to be crucial in cancer growth and advancement. This review primarily discusses the normal functions of mTOR as well as its abnormal roles in cancer development.
Article
Immunology
Francesco Tovoli, Dante Pio Pallotta, Vito Sansone, Massimo Iavarone, Massimo De Giorgio, Luca Ielasi, Giovan Giuseppe Di Costanzo, Paolo Giuffrida, Rodolfo Sacco, Tiziana Pressiani, Maria Francesca Di Donato, Franco Trevisani, Stefano Fagiuoli, Fabio Piscaglia, Alessandro Granito
Summary: This study retrospectively analyzed the characteristics and outcomes of sorafenib-treated HCC patients in a large multicenter dataset, showing that multimodal and sequential treatments are relatively frequent in post-LT HCC patients and contribute to a remarkable overall survival, together with favorable baseline characteristics.
Review
Immunology
Jun Zeng, Qiang Zhong, Xiaobing Feng, Linde Li, Shijian Feng, Yu Fan, Turun Song, Zhongli Huang, Xianding Wang, Tao Lin
Summary: Conversion from CNIs to mTORi therapy in kidney transplant recipients can improve renal function and reduce the incidence of malignancy, but is associated with a higher risk of adverse events such as acute rejection, infection, proteinuria, leukopenia, acne, and mouth ulcer, leading to increased drug discontinuation rates. The conversion strategy may be suitable for selected patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Runze Shang, Xinhua Song, Pan Wang, Yi Zhou, Xinjun Lu, Jingxiao Wang, Meng Xu, Xinyan Chen, Kirsten Utpatel, Li Che, Binyong Liang, Antonio Cigliano, Matthias Evert, Diego F. Calvisi, Xin Chen
Summary: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer with limited treatment options. Cabozantinib, an orally bioavailable multikinase inhibitor approved by the FDA for HCC patients, targets c-MET/ERK/p21/PKM2 cascade and VEGFR2-induced angiogenesis, and combination therapies with mTOR inhibitors may be effective against human HCC.
Review
Oncology
Jia Yang, Aydin Eresen, Alessandro Scotti, Kejia Cai, Zhuoli Zhang
Summary: Hepatocellular carcinoma is the most common liver malignancy in the United States. Sorafenib is an FDA-approved therapy that extends survival time for HCC patients, but only a small percentage of patients are eligible for surgery. Adoptive transfer of NK cells shows promise for clinical cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Chemistry, Medicinal
Koen G. A. M. Hussaarts, Leni van Doorn, Sander Bins, Dave Sprengers, Peter de Bruijn, Roelof W. F. van Leeuwen, Stijn L. W. Koolen, Teun van Gelder, Ron H. J. Mathijssen
Summary: The study found that sorafenib exposure decreased over time during combined treatment with immunosuppressants, and two patients also experienced declining tacrolimus plasma levels. Patients were unable to increase the sorafenib dose higher than 200 mg b.i.d. without experiencing significant toxicity.
Article
Biochemistry & Molecular Biology
Chun-Ming Ho, Kuen-Tyng Lin, Roger Shen, De-Leung Gu, Szu-Shuo Lee, Wen-Hui Su, Yuh-Shan Jou
Summary: With the increasing incidence and mortality of hepatocellular carcinoma (HCC), identifying innovative targets for therapy is crucial. In a transcriptome analysis of HCC and mouse liver cancer, concordantly expressed genes associated with patient survival were identified. Among these genes, some were found to be enriched in sorafenib-related functions and could serve as innovative targets for combination therapy with sorafenib.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Oncology
D. Araujo, A. Greystoke, S. Bates, A. Bayle, E. Calvo, L. Castelo-Branco, J. de Bono, A. Drilon, E. Garralda, P. Ivy, O. Kholmanskikh, I. Melero, G. Pentheroudakis, J. Petrie, R. Plummer, S. Ponce, S. Postel-Vinay, L. Siu, A. Spreafico, A. Stathis, N. Steeghs, C. Yap, T. A. Yap, M. Ratain, L. Seymour
Summary: In 2021, the FDA Oncology Center of Excellence launched Project Optimus to optimize dosage for oncology drugs. The MDICT Taskforce reviewed and discussed dosage optimization for oncology trials, providing recommendations for trial design and a practical guide for phase I trials. The aim is to improve dosage selection in early clinical trials of new anticancer treatments and ultimately enhance patient outcomes.
ANNALS OF ONCOLOGY
(2023)
Letter
Gastroenterology & Hepatology
Loreto Martin-Navarro, Carlos de Andrea, Bruno Sangro, Josepmaria Argemi
JOURNAL OF HEPATOLOGY
(2023)
Article
Oncology
Ines Marin, Olga Boix, Andrea Garcia-Garijo, Isabelle Sirois, Adria Caballe, Eduardo Zarzuela, Irene Ruano, Camille Stephan-Otto Attolini, Neus Prats, Jose A. Lopez-Dominguez, Marta Kovatcheva, Elena Garralda, Javier Munoz, Etienne Caron, Maria Abad, Alena Gros, Federico Pietrocola, Manuel Serrano
Summary: Senescent cells possess various features that make them highly efficient in stimulating dendritic cells and antigen-specific CD8 T cells, including the release of alarmins, activation of IFN signaling, enhanced MHC class I machinery, and presentation of specific self-peptides. Immunization with senescent cancer cells induces strong antitumor protection mediated by DCs and CD8 T cells, surpassing the effectiveness of immunization with cancer cells undergoing immunogenic cell death. Furthermore, induction of senescence in human primary cancer cells enhances their ability to activate autologous antigen-specific tumor-infiltrating CD8 lymphocytes. This study highlights the potential of exploiting senescent cancer cells to develop efficient and protective CD8-dependent antitumor immune responses.
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
Thomas Yau, Vittorina Zagonel, Armando Santoro, Mirelis Acosta-Rivera, Su Pin Choo, Ana Matilla, Aiwu Ruth He, Antonio Cubillo Gracian, Anthony B. El-Khoueiry, Bruno Sangro, Tarek E. Eldawy, Jordi Bruix, Giovanni Luca Frassineti, Gina M. Vaccaro, Marina Tschaika, Christian Scheffold, Petra Koopmans, Jaclyn Neely, Fabio Piscaglia
Summary: The study aimed to investigate the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma. The results showed that this combination therapy had promising antitumor activity and a favorable safety profile in the treatment of advanced hepatocellular carcinoma.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Daniel Aliseda, Pablo Marti-Cruchaga, Gabriel Zozaya, Macarena Rodriguez-Fraile, Jose I. Bilbao, Alberto Benito-Boillos, Antonio Martinez de la Cuesta, Luis Lopez-Olaondo, Francisco Hidalgo, Mariano Ponz-Sarvise, Ana Chopitea, Javier Rodriguez, Mercedes Inarrairaegui, Jose Ignacio Herrero, Fernando Pardo, Bruno Sangro, Fernando Rotellar
Summary: This retrospective study evaluated the postoperative and long-term survival outcomes of patients with unresectable or high biological risk HCC and ICC treated with radioembolization (RE) and subsequently rescued by liver surgery with curative intent. The results showed that liver resection after RE is safe and feasible, with good short-term outcomes. Moreover, the long-term outcomes after RE and liver resection were optimal, with a 10-year overall survival rate greater than 50% for HCC and ICC patients. The study also highlighted the efficacy of RE in downstaging or bridging to liver transplantation for HCC patients.
Article
Oncology
Maria Lozano-Rabella, Andrea Garcia-Garijo, Jara Palomero, Anna Yuste-Estevanez, Florian Erhard, Roc Farriol-Duran, Juan Martin-Liberal, Maria Ochoa-de-Olza, Ignacio Matos, Jared J. Gartner, Michael Ghosh, Francesc Canals, August Vidal, Josep Maria Piulats, Xavier Matias-Guiu, Irene Brana, Eva Munoz-Couselo, Elena Garralda, Andreas Schlosser, Alena Gros
Summary: This study investigated the immunogenicity of tumor antigens derived from noncanonical translated proteins on HLA-I. Peptides presented on HLA-I were identified in tumor cell lines from melanoma, gynecologic, and head and neck cancer through proteogenomics. 507 candidate tumor antigens, including nonC-TL, were tested for T-cell recognition, and antigen-specific T-cell receptors (TCR) were isolated and evaluated for their therapeutic potential.
CLINICAL CANCER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Bruno Sangro, Thomas Yau, Anthony B. El-Khoueiry, Masatoshi Kudo, Yun Shen, Marina Tschaika, Amit Roy, Yan Feng, Ling Gao, Urvi Aras
Summary: This analysis aimed to determine the appropriate dose selection for the combination of nivolumab plus ipilimumab in treating patients with hepatocellular carcinoma. The study found that increased exposure to ipilimumab was associated with improved tumor response and overall survival, while exposure to nivolumab had no significant impact. Adverse events related to liver and immune responses were more common in one treatment arm compared to others. Overall, the regimen of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg followed by nivolumab monotherapy 240 mg q2w showed the most favorable benefit:risk profile in advanced HCC patients.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Oncology
Michael Baumann, Julio Celis, Ulrik Ringborg, Manuel Heitor, Anton Berns, Tit Albreht, Jeliazko Arabadjiev, Michael Boutros, Mario Brandenburg, Helena Canhao, Fatima Carneiro, Christine Chomienne, Francesco De Lorenzo, Alexander M. M. Eggermont, Angel Font, Elena Garralda, Margarida Goulart, Rui Henrique, Mark Lawler, Lena Maier-Hein, Francoise Meunier, Simon Oberst, Pedro Oliveira, Maria Papatriantafyllou, Joachim Schuez, Eric Solary, Alfonso Valencia, Rosalia Vargas, Elisabete Weiderpass, Nils Wilking
Summary: European cancer research stakeholders gathered in Heidelberg, Germany, for the 5(th) Gago conference on European Cancer Policy in October 2022. The meeting focused on the current state of cancer research and care policy in Europe, identifying gaps in existing programs and proposing priorities for the future through the Heidelberg Manifesto for cancer research. The discussions in the meeting covered various aspects of cancer research, including infrastructure, digitalization, and collaboration, with an emphasis on implementation and sustainability.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Josep Tabernero, Eric Van Cutsem, Elena Garralda, David Tai, Filippo De Braud, Ravit Geva, Mark T. J. van Bussel, Katia Fiorella Dotti, Elena Elez, Maria J. de Miguel, Kevin Litwiler, Danielle Murphy, Michelle Edwards, Van Karlyle Morris
Summary: This study evaluated the maximum tolerated dose of WNT974 in combination with encorafenib and cetuximab in patients with BRAF (V600E)-mutant metastatic colorectal cancer. The results showed a high incidence of adverse events and no evidence of improved anti-tumor activity, leading to study discontinuation.
Article
Oncology
Alberto Hernando-Calvo, Oriol Mirallas, David Marmolejo, Omar Saavedra, Maria Vieito, Juan David Assaf Pastrana, Susana Aguilar, Coro Bescos, Juan Lorente, Jordi Giralt, Sergi Benavente, Jordi Temprana-Salvador, Margarita Alberola, Rodrigo Dienstmann, Elena Garralda, Enriqueta Felip, Guillermo Villacampa, Irene Brana
Summary: This study investigated the impact of clinical and pathological variables on immunotherapy outcomes in recurrent or metastatic head and neck squamous cell carcinoma patients. The results showed that variables related to the patient's nutritional status and overall condition significantly affected the treatment outcome. Therefore, nutritional status should be considered before immunotherapy.
Editorial Material
Multidisciplinary Sciences
Elena Garralda, Scott A. Laurie, Lesley Seymour, Elisabeth G. E. de Vries
Summary: Early detection of immunotherapy-induced tumor response is crucial, but therapy-induced pseudoprogression can make it complicated. A consensus guideline called iRECIST, a modification of RECIST version 1.1, was developed. This article explores the next steps required to test its validity and proposes novel approaches for response criteria.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Oncology
Alberto Hernando-Calvo, Elena Garralda
Summary: The heterogeneity of cancer molecular profiles and the variability of anticancer responses has led to the need for personalized therapies. However, the development of effective combinations of targeted therapies faces various challenges, including biomarker discovery, rational combination selection, additive toxicities, and regulatory requirements. Despite an increase in preclinical publications exploring combinations, only a few have reached routine clinical care.
Article
Oncology
H. Linardou, A. A. Adjei, J. Bajpai, S. Banerjee, A. S. Berghoff, C. Cerqueira Mathias, S. P. Choo, R. Dent, E. Felip, A. J. S. Furness, M. C. Garassino, E. Garralda, A. Konsoulova-Kirova, A. Letsch, A. M. Menzies, D. Mukherji, S. Peters, C. Sessa, J. Tsang, J. C. -H. Yang, P. Garrido
Summary: Background: Following a survey in 2016 by the European Society for Medical Oncology Women for Oncology (ESMO W4O), which revealed a significant lack of female oncologists in leadership roles, ESMO launched initiatives to address obstacles to gender equity. A follow-up survey in October 2021 assessed progress made. Results: The 2021 survey sample was larger than in 2016, with a higher number of male respondents. The percentage of respondents in managerial or leadership roles decreased significantly in 2021 compared to 2016. The importance of leadership development for women and unconscious bias increased in 2021, and more people reported workplace harassment. Ethnicity, sexual orientation, and religion were considered to have minimal impact on career opportunities, salary setting, and potential pay gap. However, gender had a significant impact on career development, especially for younger respondents and women. The top initiatives for workplace equity were work-life balance promotion, development and leadership training, and flexible working. More 2021 respondents, particularly women, supported culture and gender equity education at work compared to 2016. Conclusions: Gender remains a substantial barrier to career progression in oncology, and despite some improvements, bridging the gender gap requires further efforts. Increased reporting of workplace discrimination and inappropriate behavior is a priority concern. The W4O 2021 survey findings provide valuable evidence for future ESMO interventions to support equity and diversity in oncology career development.
Article
Gastroenterology & Hepatology
Frank Kolligs, Dirk Arnold, Rita Golfieri, Maciej Pech, Bora Peynircioglu, Thomas Pfammatter, Maxime Ronot, Bruno Sangro, Niklaus Schaefer, Geert Maleux, Graham Munneke, Helena Pereira, Bleranda Zeka, Niels de Jong, Thomas Helmberger, R. Gol, Maciej Pech, Bora Peynircioglu, Thomas Pfammatter, Maxime Ronot, Bruno Sangro, Niklaus Schaefer, Geert Maleux, Graham Munneke, Helena Pereira, Bleranda Zeka, Thomas Helmberger
Summary: This prospective observational study aimed to evaluate the effectiveness, safety, and prognostic factors of transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC). The use of partition model dosimetry was associated with improved overall survival outcomes compared to body surface area calculations. Factors such as patient health, ascites, and liver function predicted outcomes after TARE.