Article
Cell Biology
Michael J. Walsh, Courtney T. Stump, Rakeeb Kureshi, Patrick Lenehan, Lestat R. Ali, Michael Dougan, David M. Knipe, Stephanie K. Dougan
Summary: Tumors in immune equilibrium are maintained by the immune system through the involvement of interferon-y (IFNy), which plays a critical role in protecting against oncogenic or chronic viral threats. IFNy is a central node in therapy-induced immune equilibrium.
Article
Biochemistry & Molecular Biology
Nicole Baeumer, Jessica Tiemann, Annika Scheller, Theresa Meyer, Lisa Wittmann, Matias Ezequiel Gutierrez Suburu, Lilo Greune, Matthias Peipp, Neele Kellmann, Annika Gumnior, Caroline Brand, Wolfgang Hartmann, Claudia Rossig, Carsten Muller-Tidow, Dario Neri, Cristian A. Strassert, Christian Rueter, Petra Dersch, Georg Lenz, H. Phillip Koeffler, Wolfgang E. Berdel, Sebastian Baeumer
Summary: A study found that the small arginine-rich protein protamine can condense genomic DNA into the sperm head, and its high RNA binding capacity can be utilized for the spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumor-cell-specific antibodies for efficient targeting of siRNA. These nanoparticles showed promising results in treating non-small-cell lung cancer and Ewing sarcoma models.
Article
Mathematical & Computational Biology
Santiago D. Cardenas, Constance J. Reznik, Ruchira Ranaweera, Feifei Song, Christine H. Chung, Elana J. Fertig, Jana L. Gevertz
Summary: This study investigates cetuximab resistance in head and neck squamous cell carcinoma by analyzing tumor volume data obtained from patient-derived tumor xenografts. The researchers propose a mathematical model family to deduce the resistance mechanisms, finding that additional data on resistance fraction and dose escalation is required to accurately describe the resistance.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2022)
Article
Pharmacology & Pharmacy
Ying Zhao, Xin Wang, Yi Liu, Hao-Yu Wang, Jin Xiang
Summary: This review summarizes the effects of estrogen on the targets, metabolism, and resistance of anticancer drugs and describes the related pathways and underlying mechanisms. Understanding the relationship between estrogen and cancer drug therapy is crucial for developing specific treatment strategies to achieve optimal outcomes.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Sunanda Singh, Hector J. J. Gomez, Shreya Thakkar, Samara P. P. Singh, Ashutosh S. S. Parihar
Summary: Anti-neoplastic agents for cancer treatment employ various mechanisms and when combined can effectively inhibit cancer growth. However, the development of acquired drug resistance often renders these agents ineffective. This study identifies at least 24 different anti-neoplastic agents that use the STAT3 signaling pathway to develop therapeutic resistance. Targeting STAT3 in combination with existing agents may be a successful strategy to prevent or overcome drug resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Lin Zhao, Hongjie Guo, Xi Chen, Wenxin Zhang, Qiaojun He, Ling Ding, Bo Yang
Summary: Epigenetic dysregulation plays a crucial role in the development and progression of ovarian cancer, and the combination of epigenetic targeted drugs with other treatment strategies can enhance tumor sensitivity and reverse resistance. Analysis of clinical trials and future drug development strategies provides promising ideas for the application of epigenetic drugs in ovarian cancer treatment.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Yujie Zhang, Zhichao Xing, Tianyou Liu, Minghai Tang, Li Mi, Jingqiang Zhu, Wenshuang Wu, Tao Wei
Summary: This review focuses on the rapid development of treatment for advanced thyroid cancer and the study of drug resistance mechanisms. The current treatment for advanced thyroid cancer is not satisfactory due to the existence of drug resistance. Understanding the mechanisms of drug resistance in thyroid cancer is crucial for improving the effectiveness of combination therapy and promoting the development of new drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Yihui Song, Shu Wang, Min Zhao, Xinyu Yang, Bin Yu
Summary: SHP2, encoded by PTPN11, is a promising therapeutic target for cancer therapy. However, its multifaceted roles complicate drug discovery. Strategies targeting SHP2, including inhibitors, activators, and PROTAC degraders, have been developed. Protein-protein interactions between SHP2 and other adaptor proteins are also discussed. Target- and pathway-dependent combination strategies of SHP2 for cancer therapy are highlighted.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Margareta Pernar Kovac, Vanja Tadic, Juran Kralj, George E. Duran, Alessia Stefanelli, Darija Stupin Polancec, Sanja Dabelic, Niko Bacic, Maja T. Tomicic, Petra Heffeter, Branimir I. Sikic, Anamaria Brozovic
Summary: This study investigated resistance to platinum and taxane-based chemotherapy in ovarian cancer cells and the role of TUBB3 in therapy response prediction.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Chemistry, Multidisciplinary
Xia-qing Xu, Xiao-hui Pan, Ting-ting Wang, Jian Wang, Bo Yang, Qiao-jun He, Ling Ding
Summary: Abnormal activation of cyclin-dependent kinases (CDKs) leads to aberrant cell proliferation, which is a key characteristic of tumors. Targeting the activity of CDKs is a promising therapeutic strategy, but resistance to CDK4/6 inhibitors has become a challenge. Resistance may be related to alterations in other molecular events that regulate the cell cycle progression.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Cell Biology
Qizhi Liu, Cheng Xin, Yikuan Chen, Jiawen Yang, Yingying Chen, Wei Zhang, Lechi Ye
Summary: The study demonstrates that PUM1 acts as a promoter in cetuximab-resistant colon cancer cells by positively regulating DDX5 through interaction and mRNA expression. In addition, inhibition of DDX5 also leads to decreased cell proliferation in SW480R and Caco-2R cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Ke-Ren Zhang, Yu-Fei Zhang, Hui-Min Lei, Ya-Bin Tang, Chun-Shuang Ma, Qian-Ming Lv, Shi-Yi Wang, Li-Ming Lu, Ying Shen, Hong-Zhuan Chen, Liang Zhu
Summary: The study uncovered a metabolic mechanism driving resistance to EGFR TKIs by promoting cystine metabolism, and suggested AKR1B1 as a potential therapeutic target to overcome resistance to EGFR TKIs.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Medicine, General & Internal
M. M. Awad, S. Liu, I. I. Rybkin, K. C. Arbour, J. Dilly, V. W. Zhu, M. L. Johnson, R. S. Heist, T. Patil, G. J. Riely, J. O. Jacobson, X. Yang, N. S. Persky, D. E. Root, K. E. Lowder, H. Feng, S. S. Zhang, K. M. Haigis, Y. P. Hung, L. M. Sholl, B. M. Wolpin, J. Wiese, J. Christiansen, J. Lee, A. B. Schrock, L. P. Lim, K. Garg, M. Li, L. D. Engstrom, L. Waters, J. D. Lawson, P. Olson, P. Lito, S. -H. I. Ou, J. G. Christensen, P. A. Janne, A. J. Aguirre
Summary: A study of 38 patients with KRAS(G12C)-mutant cancers treated with adagrasib revealed diverse mechanisms of acquired resistance in 45% of them, including various mutations and bypass mechanisms. New therapeutic strategies are needed to overcome this drug resistance.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Oncology
Tamara Rothenburger, Dominique Thomas, Yannick Schreiber, Paul R. Wratil, Tamara Pflantz, Kirsten Knecht, Katie Digianantonio, Joshua Temple, Constanze Schneider, Hanna-Mari Baldauf, Katie-May McLaughlin, Florian Rothweiler, Berna Bilen, Samira Farmand, Denisa Bojkova, Rui Costa, Nerea Ferreiros, Gerd Geisslinger, Thomas Oellerich, Yong Xiong, Oliver T. Keppler, Mark N. Wass, Martin Michaelis, Jindrich Cinatl
Summary: Intrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/DCK substrates and non-substrates provides scope for next-line therapies after treatment failure. Understanding the mechanisms behind resistance to CNDAC can help develop more effective treatment strategies for leukemia.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Infectious Diseases
Myllena Pereira Silverio, Gabriela Bergiante Kraychete, Alexandre Soares Rosado, Raquel Regina Bonelli
Summary: Pseudomonas spp. are common microorganisms with intrinsic and acquired resistance to antimicrobial agents. This review compiles published data on antimicrobial resistance in the Pseudomonas fluorescens complex, suggesting that the resistance might be related to intrinsic features or adaptive mechanisms.
Article
Oncology
Hajrah Khawaja, Rebecca Briggs, Cheryl H. Latimer, Mustasin Rassel, Dary Griffin, Lyndsey Hanson, Alberto Bardelli, Frederica Di Nicolantonio, Simon S. McDade, Christopher J. Scott, Shauna Lambe, Manisha Maurya, Andreas U. Lindner, Jochen H. M. Prehn, Jose Sousa, Chris Winnington, Melissa J. LaBonte, Sarah Ross, Sandra Van Schaeybroeck
Summary: Novel covalent inhibitors of KRASG12C have shown limited response rates in patients with KRASG12C-mutant colorectal cancer. In this study, researchers found that the combination of AZ'1569 and a Bcl-xL inhibitor led to a dramatic and universal apoptosis, suggesting a potential therapeutic strategy for patients with KRAS G12C-mutant colorectal cancer.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Oncology
Vito Amodio, Simona Lamba, Rosaria Chila, Chiara M. Cattaneo, Benedetta Mussolin, Giorgio Corti, Giuseppe Rospo, Enrico Berrino, Claudio Tripodo, Federica Pisati, Alice Bartolini, Maria Costanza Aquilano, Silvia Marsoni, Gianluca Mauri, Caterina Marchio, Sergio Abrignani, Federica Di Nicolantonio, Giovanni Germano, Alberto Bardelli
Summary: Patients with DNA mismatch repair deficiency (MMRd) in colorectal cancer (CRC) often respond to immune checkpoint blockade therapies, while those with mismatch repair-proficient (MMRp) tumors generally do not. MMRp CRCs with variable fractions of MMRd cells may impact immune surveillance. Modulation of the MMRd fraction in MMR heterogeneous tumors can enhance their immunogenicity.
Article
Pathology
Enrico Berrino, Maria Costanza Aquilano, Emanuele Valtorta, Vito Amodio, Giovanni Germano, Marco Gusmini, Katiuscia Gizzi, Elisabetta Fenocchio, Anna Sapino, Silvia Marsoni, Andrea Sartore-Bianchi, Alberto Bardelli, Salvatore Siena, Emanuela Bonoldi, Caterina Marchio
Summary: Colorectal cancer cells often exhibit homogeneous retention or loss of mismatch repair (MMR) protein expression, but rare cases show heterogeneous patterns. In this study, 200 colorectal cancers were analyzed for MMR protein expression, resulting in three groups: proficient MMR, deficient MMR, and heterogeneous MMR expression. Heterogeneous MMR tumors were further examined and compared to the other groups, revealing differential gene expression patterns and increased tumor-infiltrating lymphocytes.
Article
Oncology
Francesca Bersani, Francesca Picca, Deborah Morena, Luisella Righi, Francesca Napoli, Mariangela Russo, Daniele Oddo, Giuseppe Rospo, Carola Negrino, Barbara Castella, Marco Volante, Angela Listi, Vanessa Zambelli, Federica Benso, Fabrizio Tabbo, Paolo Bironzo, Emanuele Monteleone, Valeria Poli, Filippo Pietrantonio, Federica Di Nicolantonio, Alberto Bardelli, Carola Ponzetto, Silvia Novello, Giorgio V. Scagliotti, Riccardo Taulli
Summary: This study demonstrates that the measurement of circMET levels in the plasma can be used to identify and track patients with high MET activity. It provides a simple, cost-effective, non-invasive approach for implementing patient stratification based on MET expression and monitoring therapy response and clonal evolution during treatment.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Valentina Comunanza, Chiara Gigliotti, Simona Lamba, Gabriella Doronzo, Edoardo Vallariello, Valentina Martin, Claudio Isella, Enzo Medico, Alberto Bardelli, Dario Sangiolo, Federica Di Nicolantonio, Federico Bussolino
Summary: The introduction of targeted therapies has greatly improved the treatment of BRAFV600E melanoma, but acquired resistance remains a challenge. This study explored the strategy of VEGFA/BRAF inhibition in immunocompetent melanoma murine models and found that it reshaped the tumor microenvironment, enhanced immune cell infiltration, and sensitized tumors to immune checkpoint blockade. Combining VEGFA/BRAF targeting with anti-PD-1 antibody resulted in a durable response and complete tumor eradication in 50% of the mice.
MOLECULAR ONCOLOGY
(2023)
Editorial Material
Oncology
Federica Di Nicolantonio, Alberto Bardelli
Summary: Allele-specific inhibitors of KRAS(G12C) have been approved for non-small-cell lung cancer. This article discusses recent results from the phase I/II KRYSTAL-1 trial of adagrasib alone and in combination with cetuximab in patients with KRAS(G12C)-mutant metastatic colorectal cancer. The combination treatment showed promising efficacy and, if confirmed in later-phase trials, simultaneous inhibition of EGFR and KRAS(G12C) will introduce a new paradigm in precision oncology.
NATURE REVIEWS CLINICAL ONCOLOGY
(2023)
Article
Cell Biology
Marta Falcinelli, Giulia Dell'Omo, Elena Grassi, Elisa Mariella, Simonetta Maria Leto, Sharon Scardellato, Annalisa Lorenzato, Sabrina Arena, Andrea Bertotti, Livio Trusolino, Alberto Bardelli, Fabrizio d'Adda di Fagagna
Summary: This study found that colorectal cancer (CRC) does not easily engage in alternative lengthening of telomeres (ALT), even with mutations in ATRX and/or DAXX genes.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Chiara Nicolazzo, Valentina Magri, Luca Marino, Francesca Belardinilli, Federica Di Nicolantonio, Gianluigi De Renzi, Salvatore Caponnetto, Michela De Meo, Giuseppe Giannini, Daniele Santini, Enrico Cortesi, Paola Gazzaniga
Summary: This study investigated the clinical and genomic features associated with RAS mutation clearance in RAS mutant mCRC patients who converted to RAS wild-type. The most commonly detected actionable mutations in neo-RAS wild-type were PIK3CA. Clearance of RAS mutations in ctDNA was associated with long-term improvement of overall survival.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Mark Lawler, Lynne Davis, Simon Oberst, Kathy Oliver, Alexander Eggermont, Anna Schmutz, Carlo La Vecchia, Claudia Allemani, Yolande Lievens, Peter Naredi, Tanja Cufer, Ajay Aggarwal, Matti Aapro, Kathi Apostolidis, Anne-Marie Baird, Fatima Cardoso, Andreas Charalambous, Michel P. Coleman, Alberto Costa, Mirjam Crul, Csaba L. Degi, Federica Di Nicolantonio, Sema Erdem, Marius Geanta, Jan Geissler, Jacek Jassem, Beata Jagielska, Bengt Jonsson, Daniel Kelly, Olaf Kelm, Teodora Kolarova, Tezer Kutluk, Grant Lewison, Francoise Meunier, Jana Pelouchova, Thierry Philip, Richard Price, Beate Rau, Isabel T. Rubio, Peter Selby, Maja Juznic Sotlar, Gilliosa Spurrier-Bernard, Jolanda C. van Hoeve, Eduard Vrdoljak, Willien Westerhuis, Urszula Wojciechowska, Richard Sullivan
Summary: Cancer research is vital for improving cancer care, and patients treated in research-active hospitals have better outcomes. However, the COVID-19 pandemic has negatively impacted cancer outcomes in Europe and set back progress by almost a decade. The Lancet Oncology European Groundshot Commission aims to use detailed data on cancer research to inform future cancer care strategies in Europe.
