Review
Allergy
Peter Valent, Cem Akin, Karin Hartmann, Andreas Reiter, Jason Gotlib, Karl Sotlar, Wolfgang R. Sperr, Lina Degenfeld-Schonburg, Dubravka Smiljkovic, Massimo Triggiani, Hans-Peter Horny, Michel Arock, Stephen J. Galli, Dean D. Metcalfe
Summary: Mast cell activation plays a crucial role in allergic reactions, inflammatory states, and mast cell activation syndromes. While there is currently no treatment approach to eradicate mast cells, long-term use of drugs that inhibit KIT function may lead to a decrease in tissue mast cells and improvement in symptoms. For patients with KIT D816V-positive mastocytosis, effective KIT inhibitors like avapritinib may be used for mast cell eradication, but potential side effects need to be considered.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Clinical Neurology
Bruno Dubois, Jesus Lopez-Arrieta, Stanley Lipschitz, Doskas Triantafyllos, Luiza Spiru, Svitlana Moroz, Olena Venger, Patrick Vermersch, Alain Moussy, Colin D. D. Mansfield, Olivier Hermine, Magda Tsolaki
Summary: The study found that the tyrosine kinase inhibitor masitinib, when administered orally, can be beneficial as an adjunct treatment for mild-to-moderate Alzheimer's disease. It showed significant improvement in cognitive and functional abilities, with side effects consistent with known information. Further research is ongoing to validate these results.
ALZHEIMERS RESEARCH & THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Robin Frobom, Erik Berglund, Craig A. Aspinwall, Weng-Onn Lui, Inga-Lena Nilsson, Catharina Larsson, Robert Branstrom
Summary: The study investigated the effects of three clinically established TKIs (imatinib, sunitinib, nilotinib) on KATP channel activity, revealing that these drugs can decrease KATP channel activity by interacting with the ATP-binding site on the channel. This interaction may contribute to some of the side effects associated with TKIs.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Hematology
Bibian M. E. Tullemans, Delia Fernandez, Alicia Veninga, Constance C. F. M. J. Baaten, Linsey J. F. Peters, Maureen J. B. Aarts, Johannes A. Eble, Elena Campello, Luca Spiezia, Paolo Simioni, Emiel P. C. van der Vorst, Paola E. J. van der Meijden, Johan W. M. Heemskerk, Marijke J. E. Kuijpers
Summary: Sunitinib inhibits collagen-induced procoagulant activity and delays fibrin formation, which is exacerbated by aspirin. Therefore, we urge awareness of the combined antiplatelet effects of TKIs with aspirin, as this may lead to an increased risk of bleeding.
THROMBOSIS AND HAEMOSTASIS
(2022)
Review
Chemistry, Analytical
Asmaa M. AboulMagd, Nada S. Abdelwahab
Summary: This review discusses the characteristics and analytical methods for determination of sunitinib malate, emphasizing the need for alternative methods that are cost-effective, require minimal sample preparation, consume less toxic solvents, and leave minimal residue. The literature also reveals a lack of research on potential drug-drug pharmacokinetic interactions.
MICROCHEMICAL JOURNAL
(2021)
Article
Oncology
Girstaute Dabkeviciute, Ellias Maccioni, Vilma Petrikaite
Summary: This study aimed to evaluate the anticancer activity of 16 new sunitinib derivatives in brain cancer cells (2D model) and spheroids (3D model). The compounds were assessed for their effects on cell viability, single-cell migration, and spheroid growth. EMAC4001 showed the highest reduction in viability for U-87MG and A-172 brain cancer cells. EMAC4001 exhibited the strongest inhibition of U-87MG cell migration, while EMAC4007 was most active in the A-172 cell line. Only sunitinib and EMAC4007 had a significant impact on spheroid growth in the respective cell lines.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Oncology
Bibian M. E. Tullemans, Sanne L. N. Brouns, Frauke Swieringa, Siamack Sabrkhany, Franchette W. P. J. van den Berkmortel, Natascha A. J. B. Peters, Peter de Bruijn, Stijn L. W. Koolen, Johan W. M. Heemskerk, Maureen J. B. Aarts, Marijke J. E. Kuijpers
Summary: This study investigated the effects of TKI sunitinib on platelet count and function. The results showed that sunitinib can cause a sustained reduction in platelet count and a decrease in platelet aggregation, which is correlated to the inhibitor levels in plasma/serum. The reduced aggregation is associated with bleeding but not disease progression.
Article
Chemistry, Medicinal
Danli Zhou, Yingying Zuo, Zhengying Pan
Summary: This study reports the development of cereblon-recruiting ITK proteolysis targeting chimeras based on a structure-based design strategy, which holds great therapeutic potential for human autoimmune diseases and T-cell malignant lymphomas. Two representative compounds, 23 and 28, demonstrated potent ITK degradation and IL-2 inhibition activities in Jurkat cells. Global proteomic profiling assays confirmed the high selectivity of compounds 23 and 28 as ITK degraders. Compound 28 exhibited efficient, rapid, and prolonged ITK degradation in mice, along with significant suppression of IL-2 secretion. It is the first effective and highly selective ITK degrader, serving as a valuable tool compound for further investigation of ITK degradation in human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Editorial Material
Genetics & Heredity
Ivona Aksentijevich
Summary: Immune responses require a delicate balance - too weak or too strong a response can cause issues. Spleen tyrosine kinase plays a crucial role in multiple signaling pathways, and its gain-of-function alterations can lead to various problems, including hypogammaglobulinemia and predisposition to B cell lymphoma.
Article
Immunology
Jiaxi Yao, Wei Xi, Xiang Chen, Ying Xiong, Yanjun Zhu, Hang Wang, Xiaoyi Hu, Jianming Guo
Summary: In patients with metastatic renal cell carcinoma, those with high mast cell density demonstrated significantly better overall survival and progression-free survival compared to those with low mast cell density. TIMs were identified as an independent prognostic factor, and combining them with the IMDC risk model improved predictive ability for patient survival. Additionally, high mast cell density cases were associated with a high density of CD8(+) and CD4(+) TILs, indicating potential anti-tumor effects.
SCANDINAVIAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Oncology
Sebastian Bauer, Robin L. Jones, Jean-Yves Blay, Hans Gelderblom, Suzanne George, Patrick Schoeffski, Margaret von Mehren, John R. Zalcberg, Yoon-Koo Kang, Albiruni Abdul Razak, Jonathan Trent, Steven Attia, Axel Le Cesne, Ying Su, Julie Meade, Tao Wang, Matthew L. Sherman, Rodrigo Ruiz-Soto, Michael C. Heinrich
Summary: This study compared the efficacy and safety of ripretinib and sunitinib in patients with advanced GIST previously treated with imatinib. The results showed that ripretinib was not superior to sunitinib in terms of progression-free survival (PFS), but it had fewer treatment-emergent adverse events and better tolerability.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Yan Sun, Liang Zhu, Pian Liu, Huan Zhang, Feng Guo, Xin Jin
Summary: In this study, researchers found that the upregulation of palmitoyl acyltransferase ZDHHC2 is associated with TKI resistance in ccRCC. ZDHHC2 mediates AGK S-palmitoylation to activate the PI3K-AKT-mTOR signaling pathway, which modulates sunitinib sensitivity. These findings suggest that targeting ZDHHC2 may improve the efficacy of sunitinib in treating ccRCC.
Article
Medicine, General & Internal
J. R. Brown, B. Eichhorst, P. Hillmen, W. Jurczak, M. Kazmierczak, N. Lamanna, S. M. O'Brien, C. S. Tam, L. Qiu, K. Zhou, M. Simkovic, J. Mayer, A. Gillespie-Twardy, A. Ferrajoli, P. S. Ganly, R. Weinkove, S. Grosicki, A. Mital, T. Robak, A. Osterborg, H. A. Yimer, T. Salmi, M. -D. -Y. Wang, L. Fu, J. Li, K. Wu, A. Cohen, M. Shadman
Summary: In a multinational phase 3 trial, zanubrutinib was found to be superior to ibrutinib in treating relapsed or refractory CLL or SLL, with better efficacy and fewer side effects.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Veterinary Sciences
Yasmin Nascimento Bernardes Coelho, Luiz Ricardo Soldi, Paulo Henrique Rosa da Silva, Caio Melo Mesquita, Luiz Renato Paranhos, Thaisa Reis dos Santos, Marcelo Jose Barbosa Silva
Summary: A systematic review of 29 studies found that dogs with mast cell tumors (MCT) treated with tyrosine kinase inhibitors (TKI) had higher overall response rates and better complete or partial responses compared to those treated with vinblastine sulfate (VBL). However, vinblastine-treated dogs had higher overall survival and progression-free survival. The study's results should be interpreted with caution due to the lack of sample standardization and inclusion of variables that may have influenced the outcomes.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Multidisciplinary Sciences
Sanjay de Mel, Nurulhuda Mustafa, Viknesvaran Selvarajan, Muhammad Irfan Azaman, Patrick William Jaynes, Shruthi Venguidessane, Hoang Mai Phuong, Zubaida Talal Alnaseri, The Phyu, Louis-Pierre Girard, Wee Joo Chng, Joanna Wardyn, Ying Li, Omer An, Henry Yang, Siok Bian Ng, Anand D. Jeyasekharan
Summary: ZAP-70 is highly expressed in T/NK lymphoma cell lines but not in B-cell lymphoma cell lines. However, silencing or overexpression of ZAP-70 does not significantly affect cell viability or proliferation. The expression and signaling of ZAP-70 in T/NK lymphoma do not appear to be critical for cell survival or downstream TCR-mediated signaling.