Review
Oncology
Sherrie Mikhaeel, Ehab Atallah
Summary: Tyrosine kinase inhibitor (TKI) discontinuation, also known as treatment-free remission (TFR), is an important goal in the therapy of chronic myeloid leukemia (CML) due to the impact of TKI therapy on quality of life, long-term side effects, and financial burden. TKI discontinuation is particularly crucial for young CML patients as it affects their growth and development. Multiple studies have demonstrated the safety and feasibility of attempting TKI discontinuation in patients with sustained deep molecular remission.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Review
Oncology
Kota Yoshifuji, Koji Sasaki
Summary: The prognosis of CML-CP has significantly improved with the introduction of imatinib. Besides imatinib, other TKIs and a novel drug asciminib are now available. Long-term TKI therapy requires individualized selection based on toxicity profile to minimize chronic toxicity and the risk of adverse events. This review summarizes the characteristics and adverse event profile of each TKI and discusses future perspectives in the treatment of CML-CP.
FRONTIERS IN ONCOLOGY
(2022)
Article
Mathematical & Computational Biology
Yuji Okamoto, Mitsuhito Hirano, Kai Morino, Masashi K. Kajita, Shinji Nakaoka, Mayuko Tsuda, Kei-ji Sugimoto, Shigehisa Tamaki, Junichi Hisatake, Hisayuki Yokoyama, Tadahiko Igarashi, Atsushi Shinagawa, Takeaki Sugawara, Satoru Hara, Kazuhisa Fujikawa, Seiichi Shimizu, Toshiaki Yujiri, Hisashi Wakita, Kaichi Nishiwaki, Arinobu Tojo, Kazuyuki Aihara
Summary: This study successfully classified CML patients with different nilotinib responses by using a dynamical model and laboratory findings. A method was proposed to identify patients who failed to achieve a treatment goal based on data collected at three initial time points only.
NPJ SYSTEMS BIOLOGY AND APPLICATIONS
(2022)
Review
Oncology
Theresa Steeb, Anja Wessely, Anne Petzold, Christoph Kohl, Michael Erdmann, Carola Berking, Markus V. Heppt
Summary: The study summarized the efficacy and safety of c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma. Results showed that c-Kit inhibitors are a valuable treatment option for patients with KIT mutant melanoma, with nilotinib having the highest objective response rate.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Pharmacology & Pharmacy
R. Ciftciler, I. C. Haznedaroglu
Summary: Philadelphia (Ph*)/BCR-A BL1-positive chronic myeloid leukemia (CML) is a neoplastic hematologic disorder that can be functionally cured using tyrosine kinase inhibitor (TKI) drugs. Factors such as individual characteristics, drug compliance, lifestyle preferences, comorbidities, and physician experience should be considered when selecting the appropriate first-line TKI for newly diagnosed CML patients.
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
(2021)
Article
Hematology
Delphine Rea, Michael J. Mauro, Carla Boquimpani, Yosuke Minami, Elza Lomaia, Sergey Voloshin, Anna Turkina, Dong-Wook Kim, Jane F. Apperley, Andre Abdo, Laura Maria Fogliatto, Dennis Dong Hwan Kim, Philipp le Coutre, Susanne Saussele, Mario Annunziata, Timothy P. Hughes, Naeem Chaudhri, Koji Sasaki, Lynette Chee, Valentin Garcia-Gutierrez, Jorge E. Cortes, Paola Aimone, Alex Allepuz, Sara Quenet, Veronique Bedoucha, Andreas Hochhaus
Summary: Asciminib demonstrated superior efficacy compared to bosutinib in treating patients with CML-CP who are resistant or intolerant to >= 2 prior TKIs, with a favorable safety profile.
Review
Oncology
Takaaki Ono
Summary: This review discusses the importance of selecting the optimal BCR-ABL1 tyrosine kinase inhibitors (TKIs) for newly diagnosed CML-CP patients, and how individualized treatment choices can be made based on factors such as patient background, treatment goals, and cost.
Article
Medicine, Research & Experimental
Massimo Breccia, Francesca Chiodi, Aurelio Pio Nardozza, Diletta Valsecchi, Valentina Perrone, Diego Sangiorgi, Elisa Giacomini, Maria Chiara Rendace, Paola Coco, Eleonora Premoli, Luca Degli Esposti
Summary: This study analyzed the economic burden for managing patients with chronic myeloid leukemia (CML) in 2nd or > 3rd lines with tyrosine kinase inhibitors (TKIs) in Italian clinical practice. The results showed that as the treatment lines increased, healthcare consumption and costs for CML patients also increased, with hospitalizations accounting for about half of the total expenditure.
ADVANCES IN THERAPY
(2023)
Review
Biochemistry & Molecular Biology
Van-An Duong, Hookeun Lee
Summary: Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics is a powerful technique for analyzing cellular, tissue, and fluid proteomes. While LC-MS/MS and data analysis techniques have been well-developed, sample preparation remains a challenging and laborious process. In this review, various methods for sample preparation in proteomics, as well as devices and methods for integrating different steps of sample preparation and peptide fractionation, are outlined and discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Yves Chalandon, Giulia Sbianchi, Luuk Gras, Linda Koster, Jane Apperley, Jenny Byrne, Urpu Salmenniemi, Henrik Sengeloev, Mahmoud Aljurf, Grzegorz Helbig, Francesca Kinsella, Goda Choi, Peter Remenyi, John A. Snowden, Marie Robin, Stig Lenhoff, Stephan Mielke, Jakob Passweg, Annoek E. C. Broers, Nicolaus Kroeger, Zeynep Arzu Yegin, Sen Mui Tan, Patrick J. Hayden, Donal P. McLornan, Ibrahim Yakoub-Agha
Summary: With the introduction of TKI, the number of allo-HCT for CP CML patients has decreased significantly. The use of 1, 2, or 3 TKI prior to allo-HCT does not affect the overall survival, progression-free survival, relapse incidence, or non-relapse mortality. However, the disease stage and KPS score significantly influence the survival and progression-free survival, emphasizing the importance of careful candidate selection and performing allo-HCT during CP1 phase.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemical Research Methods
Yumi Kwon, Paul D. Piehowski, Rui Zhao, Ryan L. Sontag, Ronald J. Moore, Kristin E. Burnum-Johnson, Richard D. Smith, Wei-Jun Qian, Ryan T. Kelly, Ying Zhu
Summary: Spatial proteomics holds great promise for revealing tissue heterogeneity, but current workflows require large sample amounts that may blur cell-type or microstructure-specific information. In this study, an improved sample preparation method was developed to enhance sample recovery and enable more precise protein analysis by integration with established techniques.
Article
Biochemical Research Methods
Feiyang Li, Ryan Karongo, Despoina Mavridou, Jeannie Horak, Adrian Sievers-Engler, Michael Laemmerhofer
Summary: Enantioselective amino acid analysis is an important technique in pharmaceutical, biomedical, and food sciences. However, simultaneously analyzing all chiral proteinogenic amino acids using a single method with one column and one condition is still challenging. In this study, an enantioselective high-performance liquid chromatography-tandem mass spectrometry (LC-MS) assay using Chiralpak QN-AX as a chiral column was developed, enabling efficient separation of D- and L-amino acids.
JOURNAL OF CHROMATOGRAPHY A
(2023)
Article
Chemistry, Analytical
Lill Dannevig Muller, Siri Foreid
Summary: A simplified and optimized high-throughput automatic sample preparation method for quantification of PEth16:0/18:1 in pre-treated frozen blood samples has been developed. The method showed good reproducibility and minimal matrix effect by adjusting liquid handling parameters. The results demonstrated high sensitivity and reliability of the method.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2022)
Article
Biochemical Research Methods
Yao Zhang, Yao Liu, Lu Tan
Summary: A UHPLC-MS/MS bioassay for simultaneous determination of methotrexate, imatinib and dasatinib has been developed and fully validated, showing high precision and accuracy in therapeutic drug monitoring.
Article
Economics
B. Muresan, C. Mamolo, J. C. Cappelleri, M. J. Postma, B. Heeg
Summary: The study found that compared with dasatinib and nilotinib, bosutinib may represent good value for money in treating 2L CP-CML patients.
APPLIED HEALTH ECONOMICS AND HEALTH POLICY
(2021)
Review
Immunology
Gabriel Osborn, Chara Stavraka, Rebecca Adams, Ahmad Sayasneh, Sharmistha Ghosh, Ana Montes, Katie E. Lacy, Rebecca Kristeleit, James Spicer, Debra H. Josephs, James N. Arnold, Sophia N. Karagiannis
Summary: This review discusses the role of tumor-associated macrophages (TAMs) in the ovarian cancer tumor microenvironment (TME) and the emerging strategies that target the contributions of these cells in tumor progression through the rational design of monoclonal antibodies (mAbs).
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Immunology
Panagiotis Karagiannis, Isabel Correa, Jitesh Chauhan, Anthony Cheung, Diana Dominguez-Rodriguez, Manuela Terranova-Barberio, Robert J. Harris, Silvia Crescioli, James Spicer, Carsten Bokemeyer, Katie E. Lacy, Sophia N. Karagiannis
Summary: The study found that innate signals can stimulate the survival and antibody production of B cells, which may help identify low-frequency antigen-reactive humoral responses.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2022)
Article
Oncology
Beth Russell, Charlotte Moss, Eirini Tsotra, Charalampos Gousis, Debra Josephs, Deborah Enting, Christina Karampera, Muhammad Khan, Jose Roca, Ailsa Sita-Lumsden, Kasia Owczarczyk, Harriet Wylie, Anna Haire, Daniel Smith, Kamarul Zaki, Angela Swampillai, Mary Lei, Vishal Manik, Vasiliki Michalarea, Rebecca Kristeleit, Anca Mera, Elinor Sawyer, Lucy Flanders, Irene De Francesco, Sophie Papa, Paul Ross, James Spicer, Bill Dann, Vikash Jogia, Nisha Shaunak, Hartmut Kristeleit, Anne Rigg, Ana Montes, Mieke Van Hemelrijck, Saoirse Dolly
Summary: This study found that cancer treatment during the COVID-19 pandemic did not significantly increase mortality rates. The infection and death rates were low, but there was a reduction in treatment for later lines of palliative care. These findings can provide reassurance for the continuation of cancer treatment during the pandemic.
Review
Cell Biology
Jitesh Chauhan, Chara Stavraka, Melanie Grandits, Lais C. G. F. Palhares, Debra H. Josephs, Katie E. Lacy, James Spicer, Heather J. Bax, Sophia N. Karagiannis
Summary: Basophils, despite their small proportion in circulating blood leukocytes, play significant roles as potent immune effector cells. They express high-affinity receptors for IgE and store powerful inflammatory mediators ready to be secreted. They are implicated in allergic diseases, hypersensitivity reactions, chronic inflammation, and responses to infections. Despite their activation by Th2-biased signals, which are also observed in certain tumors, basophils have been neglected in cancer research. This article discusses the presence and functional significance of basophils in cancer patients and the tumor microenvironment, exploring gene expression analyses and the potential use of basophil activation test (BAT) to predict hypersensitivity to cancer treatments and monitor patient desensitization.
Review
Radiology, Nuclear Medicine & Medical Imaging
Daniel J. Hughes, Manil Subesinghe, Benjamin Taylor, Andrea Bille, James Spicer, Sophie Papa, Vicky Goh, Gary J. R. Cook
Summary: Immunotherapy has greatly improved the treatment of many cancers, but patient selection and the accuracy of predictive biomarkers remain challenges. Molecular imaging shows potential in assessing treatment response, guiding personalized therapy, and monitoring immune-related toxicities.
Article
Oncology
Heather J. Bax, Jitesh Chauhan, Chara Stavraka, Aida Santaolalla, Gabriel Osborn, Atousa Khiabany, Melanie Grandits, Jacobo Lopez-Abente, Lais C. G. F. Palhares, Charleen Chan Wah Hak, Alexandra Robinson, Amy Pope, Natalie Woodman, Cristina Naceur-Lombardelli, Sadek Malas, Jack E. M. Coumbe, Mano Nakamura, Roman Laddach, Silvia Mele, Silvia Crescioli, Anna M. Black, Sara Lombardi, Silvana Canevari, Mariangela Figini, Ahmad Sayasneh, Sophia Tsoka, Kevin FitzGerald, Cheryl Gillett, Sarah Pinder, Mieke Van Hemelrijck, Rebecca Kristeleit, Sharmistha Ghosh, Ana Montes, James Spicer, Sophia N. Karagiannis, Debra H. Josephs
Summary: This study investigated the potential use of sFR alpha as a biomarker for ovarian cancer. The results showed that sFR alpha levels were significantly higher in patients compared to healthy volunteers and decreased alongside tumor burden during treatment. Additionally, high concentrations of sFR alpha reduced the effectiveness of anti-FR alpha antibodies, but this effect could be overcome by increasing antibody doses.
BRITISH JOURNAL OF CANCER
(2023)
Editorial Material
Immunology
Ammara Masood, Amanda Mootoo, Panayiotis Maghsoudlou, David D'Cruz, Krishnie Srikandarajah, Mark Harries, Nicholas Hart, Sophie Papa, James Spicer
AUTOIMMUNITY REVIEWS
(2023)
Article
Oncology
Cienne Morton, Richard Sullivan, Debashis Sarker, John Posner, James Spicer
Summary: The COVID-19 pandemic has posed a significant threat to cancer patients, impacting their standard care and disrupting clinical trials. However, it has also provided an opportunity for positive reforms in clinical cancer research, as the lessons learned from streamlining processes during the pandemic can be applied to improve the traditionally complex approval, trial design, procedures, and data collection in cancer research.
BRITISH JOURNAL OF CANCER
(2023)
Article
Multidisciplinary Sciences
Silvia Crescioli, Isabel Correa, Joseph Ng, Zena N. Willsmore, Roman Laddach, Alicia Chenoweth, Jitesh Chauhan, Ashley Di Meo, Alexander Stewart, Eleni Kalliolia, Elena Alberts, Rebecca Adams, Robert J. Harris, Silvia Mele, Giulia Pellizzari, Anna B. M. Black, Heather J. Bax, Anthony Cheung, Mano Nakamura, Ricarda M. Hoffmann, Manuela Terranova-Barberio, Niwa Ali, Ihor Batruch, Antoninus Soosaipillai, Ioannis Prassas, Antigona Ulndreaj, Miyo K. Chatanaka, Rosamund Nuamah, Shichina Kannambath, Pawan Dhami, Jenny L. C. Geh, Alastair D. MacKenzie Ross, Ciaran Healy, Anita Grigoriadis, David Kipling, Panagiotis Karagiannis, Deborah K. Dunn-Walters, Eleftherios P. Diamandis, Sophia Tsoka, James Spicer, Katie E. Lacy, Franca Fraternali, Sophia N. Karagiannis
Summary: B cells play an important role in the anti-tumor immune response in immunogenic tumors such as melanoma. Tumor-associated B cells undergo clonal expansion, class switch recombination, somatic hypermutation, and receptor revision. Tumor-associated B cells produce antibodies with higher levels of unproductive sequences and distinct complementarity determining region 3 properties. These findings suggest the presence of an active and aberrant autoimmune-like reaction in the tumor microenvironment.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jitesh Chauhan, Melanie Grandits, Lais C. G. F. Palhares, Silvia Mele, Mano Nakamura, Jacobo Lopez-Abente, Silvia Crescioli, Roman Laddach, Pablo Romero-Clavijo, Anthony Cheung, Chara Stavraka, Alicia M. M. Chenoweth, Heng Sheng Sow, Giulia Chiaruttini, Amy E. E. Gilbert, Tihomir Dodev, Alexander Koers, Giulia Pellizzari, Kristina M. M. Ilieva, Francis Man, Niwa Ali, Carl Hobbs, Sara Lombardi, Daniel A. Lionarons, Hannah J. J. Gould, Andrew J. J. Beavil, Jenny L. C. Geh, Alastair D. MacKenzie D. Ross, Ciaran Healy, Eduardo Calonje, Julian Downward, Frank O. O. Nestle, Sophia Tsoka, Debra H. H. Josephs, Philip J. J. Blower, Panagiotis Karagiannis, Katie E. E. Lacy, James Spicer, Sophia N. N. Karagiannis, Heather J. J. Bax
Summary: Despite checkpoint inhibitor therapies, outcomes for 50% of melanoma patients remain poor. Melanoma-associated antigen CSPG4 is expressed in approximately 70% of cases, making it a potential target for effective immunotherapies. Using monoclonal IgE antibodies engineered with human constant domains to recognize CSPG4, we found that IgE binds to human melanomas, induces antibody-dependent cellular cytotoxicity, and stimulates pro-inflammatory responses in Fc-receptor-expressing monocytes. IgE demonstrates anti-tumor activity in melanoma xenograft models, enhancing macrophage infiltration and pro-inflammatory signaling pathways in the tumor microenvironment. Our findings suggest that IgE-based immunotherapy holds promise for melanoma treatment.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Sophie Papa, Antonella Adami, Michael Metoudi, Richard Beatson, Molly Sarah George, Daniela Achkova, Evangelia Williams, Sefina Arif, Fiona Reid, Maria Elstad, Nicholas Beckley-Hoelscher, Abdel Douri, Marc Delord, Mike Lyne, Dharshene Shivapatham, Christopher Fisher, Andrew Hope, Sakina Gooljar, Arindam Mitra, Linda Gomm, Cienne Morton, Rhonda Henley-Smith, Selvam Thavaraj, Alice Santambrogio, Cynthia Andoniadou, Sarah Allen, Victoria Gibson, Gary J. R. Cook, Ana C. Parente-Pereira, David M. Davies, Farzin Farzaneh, Anna Schurich, Teresa Guerrero-Urbano, Jean-Pierre Jeannon, James Spicer, John Maher
Summary: This study developed an autologous CD28-based chimeric antigen receptor T-cell (CAR-T) therapy named T4 immunotherapy for locally advanced/recurrent head and neck squamous cell carcinoma (HNSCC). Patient-derived T-cells were engineered to express a panErbB-specific CAR and an IL-4-responsive chimeric cytokine receptor. Intratumoral delivery was used to mitigate off-tumor toxicity. The study demonstrated the safe and effective intratumoral administration of T4 immunotherapy in advanced HNSCC.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Multidisciplinary Sciences
James Spicer, Bristi Basu, Ana Montes, Udai Banerji, Rebecca Kristeleit, Rowan Miller, Gareth J. J. Veal, Christopher J. J. Corrigan, Stephen J. J. Till, Mariangela Figini, Silvana Canevari, Claire Barton, Paul Jones, Sarah Mellor, Simon Carroll, Chris Selkirk, George Nintos, Vineet Kwatra, Ionut-Gabriel Funingana, Gary Doherty, Hannah J. J. Gould, Giulia Pellizzari, Mano Nakamura, Kristina M. M. Ilieva, Atousa Khiabany, Chara Stavraka, Jitesh Chauhan, Cheryl Gillett, Sarah Pinder, Heather J. J. Bax, Debra H. H. Josephs, Sophia N. N. Karagiannis
Summary: The study reports the results of a phase I dose escalation trial of MOv18 IgE, a chimeric first-in-class IgE antibody, in patients with tumours expressing folate receptor-alpha. The most common toxicity observed was transient urticaria and evidence of anti-tumour activity was observed in a patient with ovarian cancer.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Ehsan Ghorani, Matteo Quartagno, Fiona Blackhall, Duncan C. Gilbert, Mary O'Brien, Christian Ottensmeier, Elena Pizzo, James Spicer, Alex Williams, Philip Badman, Mahesh K. B. Parmar, Michael J. Seckl
Summary: Some immunotherapy dosing regimens for advanced cancer patients may result in overtreatment, and new approaches are needed to reduce unnecessary treatment. REFINE-Lung is a UK multicentre phase 3 study that uses a novel design to determine the optimal dose frequency of pembrolizumab.
Article
Oncology
Hedy L. Kindler, Silvia Novello, Alessandra Bearz, Giovanni L. Ceresoli, Joachim G. J. Aerts, James Spicer, Paul Taylor, Kristiaan Nackaerts, Alastair Greystoke, Ross Jennens, Luana Calabro, Jacobus A. Burgers, Armando Santoro, Susana Cedres, Piotr Serwatowski, Santiago Ponce, Jan P. Van Meerbeeck, Anna K. Nowak, George Biumenschein, Jonathan M. Siegel, Linda Kasten, Karl Koechert, Annette O. Walter, Barrett H. Childs, Cem Elbi, Raffit Hassan, Dean A. Fennell
Summary: In second-line treatment of malignant pleural mesothelioma, the antibody-drug conjugate anetumab ravtansine showed similar safety and no superiority compared to vinorelbine.
Article
Oncology
Giuseppe Luigi Banna, Alfredo Addeo, Panagiota Zygoura, Zoi Tsourti, Sanjay Popat, Alessandra Curioni-Fontecedro, Ernest Nadal, Riyaz Shah, Anthony Pope, Patricia Fisher, James Spicer, Amy Roy, David Gilligan, Oliver Gautschi, Wolf-Dieter Janthur, Rafael Lopez-Castro, Heidi Roschitzki-Voser, Urania Dafni, Solange Peters, Rolf A. Stahel
Summary: This study aimed to identify clinical and laboratory parameters associated with treatment response in patients with relapsed MPM. The results showed that high SII and low hemoglobin levels were associated with worse progression-free survival. A mesothelioma risk score based on these two factors was constructed to stratify patients' prognosis.