Article
Cell Biology
Tian-Yi Jiang, Xiao-Wen Cui, Tian-Mei Zeng, Yu-Fei Pan, Yun-Kai Lin, Xiao-fan Feng, Ye-Xiong Tan, Zhen-gang Yuan, Li-Wei Dong, Hong-Yang Wang
Summary: The deficiency of PTEN is correlated with the improved efficacy of gemcitabine-based chemotherapy in cholangiocarcinoma (CCA). PTEN deficiency or down-regulation enhances gemcitabine efficacy by directly binding to and dephosphorylating the catalytic subunit of protein phosphatase 2A (PP2Ac), leading to increased enzymatic activity and diminished phosphorylation of deoxycytidine kinase (DCK). Thus, PTEN deficiency and high phosphorylation of DCK can predict a better response to gemcitabine-based chemotherapy in CCA.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Alireza Abbaspour, Mehdi Dehghani, Mahtab Setayesh, Marjan Tavakkoli, Hossein Ali Rostamipour, Marziyeh Ghorbani, Mani Ramzi, Shapour Omidvari, Fatemeh Moosavi, Omidreza Firuzi
Summary: This study aimed to assess the power of serum CDA residual activity in predicting drug efficacy and toxicity in gemcitabine-treated cancer patients. The results showed that CDA activity was associated with patient survival and the occurrence of anemia.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2023)
Article
Oncology
Masahiro Yamamoto, Tomomi Sanomachi, Shuhei Suzuki, Hiroyuki Uchida, Hajime Yonezawa, Nayuta Higa, Tomoko Takajo, Yuki Yamada, Asuka Sugai, Keita Togashi, Shizuka Seino, Masashi Okada, Yukihiko Sonoda, Hirofumi Hirano, Koji Yoshimoto, Chifumi Kitanaka
Summary: The study found that hENT1 and dCK expression levels in high-grade meningioma cells are closely related to tumor cell proliferative activity and patient survival. These results highlight the critical roles of hENT1 and dCK in the growth and gemcitabine sensitivity of meningioma cells.
Article
Oncology
Hai Yang, Bin Liu, Dongxue Liu, Zhirong Yang, Shuman Zhang, Pengyan Xu, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, Nathalie Britzen-Laurent, Robert Gruetzmann, Christian Pilarsky
Summary: Pancreatic cancer is a highly lethal cancer with limited treatment options. Chemotherapy, especially with gemcitabine, is the primary choice for patients; however, chemoresistance presents a significant challenge to its effectiveness. In this study, we used genome-wide CRISPR/Cas9 screening to identify DCK and CCNL1 as genes contributing to gemcitabine resistance in pancreatic cancer. Furthermore, we explored the mechanism of CCNL1-related resistance and found that the loss of CCNL1 activates the ERK/AKT/STAT3 pathway, leading to resistance to gemcitabine.
Article
Biochemical Research Methods
Emma K. Davison, David A. Petrone, Michael Meanwell, Matthew B. Nodwell, Steven M. Silverman, Louis-Charles Campeau, Robert Britton
Summary: This protocol presents a novel method for the synthesis of nucleoside analogs, addressing several challenges and allowing for flexible and selective access to these valuable compounds from simple starting materials.
Article
Chemistry, Organic
Mateus Mittersteiner, Genilson S. Pereira, Yuri Silva, Ludger A. Wessjohann, Helio G. Bonacorso, Marcos A. P. Martins, Nilo Zanatta
Summary: Selective N- or O-alkylation of 4-(trihalomethyl)-pyrimidin-2(1H)-ones using 5-bromo enones/enaminones as alkylating agents is reported. The selectivity towards the N- or O-regioisomer is determined by the substituent at the 6-position of the pyrimidine ring, allowing the preparation of each isomer as the sole product in yields of 60-95%. Subsequent cyclocondensation of the enaminone moiety with nitrogen dinucleophiles leads to pyrimidine-azole conjugates with yields of 55-83%.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Cell Biology
Ting Li, Zhonghua Tao, Yihui Zhu, Xiaojia Liu, Leiping Wang, Yiqun Du, Jun Cao, Biyun Wang, Jian Zhang, Xichun Hu
Summary: Exosomes derived from resistant cancer cells induce gemcitabine resistance in triple-negative breast cancer cells through upregulating ANXA6 expression, which is associated with the inhibition of EGFR ubiquitination and degradation. Exosomal ANXA6 levels in the serum of patients with TNBC may serve as a predictive factor for response to gemcitabine-based chemotherapy.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Julian Peter Mueller, Dirk Gruendemann
Summary: In this study, it has been demonstrated that the ergothioneine transporter ETT does not transport nucleosides but efficiently transports gemcitabine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Satish Sagar, Pramila D. Leiphrakpam, Divya Thomas, Kyle L. McAndrews, Thomas C. Caffrey, Benjamin J. Swanson, Henrik Clausen, Hans H. Wandall, Michael A. Hollingsworth, Prakash Radhakrishnan
Summary: The study demonstrates that MUC4 enhances tumorigenesis in PDAC, increasing malignant properties and gemcitabine resistance through altering signaling pathways and expression of nucleoside transporters.
Article
Oncology
Elisabeth S. Stovgaard, Karama Asleh, Nazia Riaz, Samuel Leung, Dongxia Gao, Lise B. Nielsen, Anne-Vibeke Laenkholm, Eva Balslev, Maj-Britt Jensen, Dorte Nielsen, Torsten Nielsen
Summary: This study found that in non-luminal breast cancers, patients with low FOXP3+ TILs may significantly benefit from treatment with gemcitabine + docetaxel (GD).
Article
Chemistry, Medicinal
Chih-Wei Fu, Han-En Tsai, Wei-Sheng Chen, Tzu-Ting Chang, Chia-Ling Chen, Pei-Wen Hsiao, Wen-Shan Li
Summary: Our study reports the synthesis and evaluation of a series of cell-permeable and N- versus O-selective sialyltransferase inhibitors. Among them, FCW34 and FCW66 were shown to effectively inhibit cell migration, with FCW34 also demonstrating inhibitory effects on tumor growth, angiogenesis, and cancer cell metastasis.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Engineering, Biomedical
Bijay Singh, Sushila Maharjan, Daniel C. Pan, Zongmin Zhao, Yongsheng Gao, Yu Shrike Zhang, Samir Mitragotri
Summary: Monotherapy with a single chemotherapeutic regimen has faced challenges in terms of clinical efficacy, leading to the need for combination therapy. This study demonstrates the potential of a hyaluronic acid-based drug combination of gemcitabine with imiquimod to stimulate immune cells and suppress breast cancer growth.
Article
Pharmacology & Pharmacy
Verona Buocikova, Silvia Tyciakova, Eleftherios Pilalis, Chara Mastrokalou, Maria Urbanova, Miroslava Matuskova, Lucia Demkova, Veronika Medova, Eleonora Marta Longhin, Elise Runden-Pran, Maria Dusinska, Ivan Rios-Mondragon, Mihaela Roxana Cimpan, Alena Gabelova, Andrea Soltysova, Bozena Smolkova, Aristotelis Chatziioannou
Summary: DAC, in combination with traditional anticancer drugs, shows promise as a treatment option for solid tumors. Increasing DCK expression to potentiate DAC's effect did not lead to changes in global DNA methylation levels or cell viability.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Oncology
Naotake Funamizu, Masahiko Honjo, Kei Tamura, Katsunori Sakamoto, Kohei Ogawa, Yasutsugu Takada
Summary: This review summarizes the current evidence for the role of microRNAs (miRNAs) in the mechanism of chemoresistance in pancreatic cancer. Pancreatic cancer has a poor prognosis due to its late discovery, aggressive nature, and chemoresistance. Aberrant miRNAs have been found to induce chemoresistance in pancreatic cancer, but the exact molecular mechanisms are still unclear. Novel biomarkers and therapeutic strategies for chemoresistance are urgently needed to improve patient outcomes.
Article
Chemistry, Multidisciplinary
Zhongming Cheng, Tilong Yang, Can Li, Yunshun Deng, Fangjia Zhang, Pinhong Chen, Zhenyang Lin, Shengming Ma, Guosheng Liu
Summary: This study presents a copper-catalyzed radical relay strategy for the site-selective cyanation of sp(2) C-H bonds in allenes. The reactions show broad substrate scope and remarkable functional group compatibility under mild conditions. The site-selectivity is attributed to the unique pocket created by the Cu-bound nitrogen-centered radical and the crucial hydrogen bonding between the fluoride and the hydrogen atom. Late-stage functionalization of drug-like bioactive molecules containing an allene motif becomes feasible.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Gastroenterology & Hepatology
Cun Wang, Hui Wang, Cor Lieftink, Aimee du Chatinier, Dongmei Gao, Guangzhi Jin, Haojie Jin, Roderick L. Beijersbergen, Wenxin Qin, Rene Bernards
Article
Oncology
Andreas Schlicker, Architha Ellappalayam, Ines J. Beumer, Mireille H. J. Snel, Lorenza Mittempergher, Begona Diosdado, Christa Dreezen, Sun Tian, Ramon Salazar, Fotios Loupakis, Filippo Pietrantonio, Cristina Santos Vivas, Maria Mercedes Martinez-Villacampa, Alberto Villanueva, Xavier Sanjuan, Marta Schirripa, Matteo Fassan, Antonia Martinetti, Giovanni Fuca, Sara Lonardi, Ulrich Keilholz, Annuska M. Glas, Rene Bernards, Loredana Vecchione
INTERNATIONAL JOURNAL OF CANCER
(2020)
Article
Oncology
Sun Tian, Fulong Wang, Shixun Lu, Gong Chen
Summary: A new supervised learning method IML was used to identify two gene expression subgroups related to FOLFOX resistance in colorectal cancer, showing that different DNA damage repair proteins are involved in these subgroups. The study also found that a subgroup of mesenchymal subtype patients benefited from FOLFOX, suggesting that personalized treatments may be needed for different FOLFOX nonresponder subgroups.
CANCER INVESTIGATION
(2021)
Review
Oncology
Giulia De Conti, Matheus Henrique Dias, Rene Bernards
Summary: Drug resistance is a major obstacle in cancer therapy, with drug-tolerant persister cells playing a key role in resisting treatment. Designing specific therapies to prevent drug resistance development is a challenge, focusing on the characteristics and evolution of these drug-tolerant persister cells.
Review
Oncology
Matheus Henrique Dias, Rene Bernards
Summary: Paradoxical interventions deliberately reinforce pathological behavior in psychotherapy to improve clinical condition. Targeted cancer therapies can selectively inhibit activated oncogenic pathways, but in advanced cancers, they provide only modest benefits due to resistance.
MOLECULAR ONCOLOGY
(2021)
Review
Oncology
Federica Di Nicolantonio, Pietro Paolo Vitiello, Silvia Marsoni, Salvatore Siena, Josep Tabernero, Livio Trusolino, Rene Bernards, Alberto Bardelli
Summary: Progress in precision medicine for colorectal cancer has been slower compared to other solid tumor types, but novel targeted therapy strategies based on tumor biology are emerging due to better translational models. The availability of patient-derived CRC models and in vitro/in vivo analyses has led to significant advances in the field over the past decade. Successful personalized treatment in CRC now involves considering the intrinsic biology of CRC cells in addition to molecular profiles of individual tumors.
NATURE REVIEWS CLINICAL ONCOLOGY
(2021)
Review
Gastroenterology & Hepatology
Cun Wang, Ying Cao, Chen Yang, Rene Bernards, Wenxin Qin
Summary: Functional genetic screens play a crucial role in uncovering new genes, identifying therapeutic targets, and guiding the development of new therapeutic strategies in liver cancer biology.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Sun Tian, Fulong Wang, Rongxin Zhang, Gong Chen
Summary: A colorectal cancer-specific method, TMEPRE, has been developed to predict cancer immunotherapy response by modeling characteristics of CD8(+) T-cell infiltration and exhaustion state. Research indicates that some MSS patients could potentially benefit from anti-PD1 treatment, whereas MSI patients with anti-PD1 resistance due to insufficient infiltration or terminal exhaustion of CD8(+) T cells may require different treatment strategies.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Barbara Steurer, Roel C. Janssens, Marit E. Geijer, Fernando Aprile-Garcia, Bart Geverts, Arjan F. Theil, Barbara Hummel, Martin E. van Royen, Bastiaan Evers, Rene Bernards, Adriaan B. Houtsmuller, Ritwick Sawarkar, Jurgen Marteijn
Summary: DNA damage inhibits RNA polymerase II from elongating, but also triggers genome-wide transcriptional responses. Particularly, promoter-bound Pol II is degraded in a GSK3 signaling-mediated response, which is crucial for cells to cope with DNA damage-induced transcription stress.
NATURE COMMUNICATIONS
(2022)
Letter
Cell Biology
Xuhui Ma, Shanshan Wu, Botai Li, Qianqian Zhang, Jianming Zhang, Wenming Liu, Hexin Yan, Rene Bernards, Wenxin Qin, Cun Wang
Review
Biotechnology & Applied Microbiology
Haojie Jin, Liqin Wang, Rene Bernards
Summary: In the past two decades, advancements in understanding the genetic defects underlying cancer have led to the development of numerous targeted cancer drugs. However, resistance to single-agent therapies remains a major hurdle. Rational drug combinations based on a deep understanding of the molecular mechanisms associated with therapy resistance hold great potential in cancer treatment. This article discusses the mechanisms of resistance to targeted therapies and the identification of effective drug combinations to overcome resistance, as well as the challenges in clinically developing these combinations and future perspectives.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Review
Gastroenterology & Hepatology
Chen Yang, Hailin Zhang, Linmeng Zhang, Andrew X. Zhu, Rene Bernards, Wenxin Qin, Cun Wang
Summary: This review summarizes the latest clinical advances in the treatment of advanced hepatocellular carcinoma, including molecular-targeted monotherapies, immuno-oncology monotherapies, combination therapies and novel therapeutic approaches.
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
(2023)
Article
Oncology
Rene Bernards
Summary: The emergence of new targeted cancer drugs necessitates a complete overhaul in the design of early clinical trials. Rene Bernards explores the need for novel clinical trial designs and the ongoing efforts to achieve this. These innovative trials have the potential to provide similar outcomes for cancer patients with reduced side effects and a decreased cost of cancer care.
MOLECULAR ONCOLOGY
(2023)
Editorial Material
Oncology
Kevin M. Ryan, Jane Smith, Rene Bernards
Summary: The formation of organizations and societies in scientific research facilitates communication, collaboration, and career development. Partnerships between organizations can further enhance these benefits. This article highlights a new partnership between the European Association for Cancer Research (EACR) and Molecular Oncology, a journal owned by the Federation of European Biochemical Societies (FEBS).
MOLECULAR ONCOLOGY
(2023)
Review
Oncology
Liqin Wang, Lina Lankhorst, Rene Bernards
Summary: This review discusses how senescence can be induced in cancer cells and how the distinctive features of senescent cancer cells can be exploited for selective eradication. It also explores activation of the host immune system as an attractive way to clear senescent cancer cells, and the potential benefits of a sequential treatment approach with pro-senescence therapy followed by senolytic therapy.
NATURE REVIEWS CANCER
(2022)