Review
Oncology
Danling Gu, Hanning Tang, Jiazhu Wu, Jianyong Li, Yi Miao
Summary: B cell receptor signaling plays a key role in the pathogenesis of B cell malignancies, with Bruton tyrosine kinase (BTK) being a critical component. While covalent BTK inhibitors have shown significant efficacy, acquired resistance and adverse events necessitate the exploration of alternative therapeutic options. Non-covalent BTK inhibitors may provide an effective choice, especially for patients who have developed resistance to covalent inhibitors.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Review
Oncology
Andrew H. Lipsky, Nicole Lamanna
Summary: Targeted therapies have revolutionized the frontline treatment for CLL, reducing reliance on chemoimmunotherapy. Drugs such as ibrutinib, acalabrutinib, and venetoclax have shown efficacy in oral therapy. This review explores novel therapeutic strategies using these agents in combination, highlighting the importance of patient characteristics and study methodology.
Review
Oncology
Hussein A. Abbas, William G. Wierda
Summary: Acalabrutinib, as a validated BTK target for B-cell malignancies, has emerged as a standard of care for these diseases, gaining approval in the US for treatment of mantle cell lymphoma and chronic lymphocytic leukemia. Clinical trial results have shown that acalabrutinib has improved efficacy and tolerable safety profile in patients with these malignancies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiu-Juan Liu, Xu Liu, Xiao-Jing Pang, Xin-Ying Yuan, Guang-Xi Yu, Yin-Ru Li, Yong-Feng Guan, Yan-Bing Zhang, Jian Song, Qiu-Rong Zhang, Sai-Yang Zhang
Summary: Bruton tyrosine kinase (BTK) plays a key role in B cell antigen receptor signaling pathway and is an important target for treating hematological malignancies and autoimmune diseases. While first-generation BTK inhibitor, Ibrutinib, has contributed significantly to the treatment of B cell malignant tumors, issues such as resistance and miss-target mutations remain. Therefore, there is an urgent need to develop novel BTK inhibitors to address these challenges.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Review
Hematology
Alexey V. Danilov, Daniel O. Persky
Summary: Advancements in understanding the disease progression of haematological malignancies have led to the development of novel targeted therapies, such as acalabrutinib, which show promise in improving treatment outcomes for patients with CLL/SLL and MCL. With its high selectivity and potential to reduce off-target toxicity, it has gained accelerated approval for clinical use and has demonstrated efficacy in phase 3 trials.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Health Care Sciences & Services
Katharine L. Lewis, Chan Y. Cheah
Summary: The B-cell receptor signalling pathway is crucial in the development of B-cell malignancies, with Bruton's tyrosine kinase (BTK) activation as a central element. While covalent BTK inhibitors have revolutionized treatment, issues such as adverse events and resistance have led to the exploration of non-covalent BTK inhibitors as an alternative therapeutic option. These non-covalent BTK inhibitors offer promise for patients intolerant to or experiencing disease progression with traditional covalent BTK inhibitors.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Immunology
Mohamed E. Shaker, Hesham A. M. Gomaa, Mohamed A. Abdelgawad, Mohamed El-Mesery, Ahmed A. Shaaban, Sara H. Hazem
Summary: This review discusses the impact of inflammation on liver diseases and the role of TLRs, such as TLR4 and TLR9, in liver diseases. It also explores the functions of tyrosine kinases (TKs) and their regulation in hepatic inflammation. The review highlights the importance of studying the role of these TKs in order to develop new therapeutic approaches for liver diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Review
Chemistry, Medicinal
Edgar Carnero Contentti, Jorge Correale
Summary: Multiple sclerosis is a chronic inflammatory disease of the central nervous system. B cells and myeloid cells play key roles in the development of the disease. BTK inhibitors show promise as novel therapeutic approaches for multiple sclerosis.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2022)
Article
Hematology
Constantine S. Tam, Stephen Opat, David Simpson, Gavin Cull, Javier Munoz, Tycel J. Phillips, Won Seog Kim, Simon Rule, Siminder Kaur Atwal, Rachel Wei, William Novotny, Jane Huang, Michael Wang, Judith Trotman
Summary: Zanubrutinib showed good tolerability and activity in patients with relapsed/refractory mantle cell lymphoma, with an overall response rate of 84% and a median progression-free survival of 21.1 months.
Article
Hematology
Paolo Strati, Morton Coleman, Rebecca Champion, Shuo Ma, Caterina Patti, Moshe Y. Levy, Izidore S. Lossos, Praveen Ramakrishnan Geethakumari, Selay Lam, Roser Calvo, Kara Higgins, Lihua E. Budde
Summary: Acalabrutinib showed greater selectivity and improved safety compared to ibrutinib in patients with relapsed/refractory chronic lymphocytic leukaemia. In patients with relapsed/refractory marginal zone lymphoma, acalabrutinib demonstrated significant efficacy and tolerability.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Review
Chemistry, Medicinal
Asim Najmi, Neelaveni Thangavel, Anugeetha Thacheril Mohanan, Marwa Qadri, Mohammed Albratty, Safeena Eranhiyil Ashraf, Safaa Fathy Saleh, Maryam Nayeem, Syam Mohan
Summary: BTK plays a crucial role in B-cell receptor signaling and is involved in B-cell malignancies and autoimmune diseases. This review examines the structural compatibility between BTK-kinase domain and its inhibitors based on recent inhibitor-bound BTK structures in the protein data bank. The study also investigates the effects of BTK on B-cell development and antibody production. Covalent inhibitors stabilize the inactive conformation of BTK by forming a bond with Cys481, while non-covalent inhibitors bind to Tyr551 in the activation kink to determine BTK selectivity. Understanding the structural complementarity of BTK and its inhibitors can aid in drug optimization and the development of therapies for B-cell malignancies and autoimmune diseases.
Review
Oncology
Stephen Jolles, Sergio Giralt, Tessa Kerre, Hillard M. Lazarus, S. Shahzad Mustafa, Roberto Ria, Donald C. Vinh
Summary: This study conducted a systematic literature review on the potential association between various cancer regimens and infection rates, neutropenia, lymphocytopenia, or hypogammaglobulinemia, which are indicative of secondary immunodeficiency. The results showed that patients with chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin lymphoma have a high risk of developing secondary immunodeficiency, related infections, and mortality.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Sarah Nocco, Tyler M. Andriano, Arpita Bose, Marina Chilov, Kendra Godwin, George Dranitsaris, Shenhong Wu, Mario E. Lacouture, Lindsay E. Roeker, Anthony R. Mato, Alina Markova
Summary: This study systematically reviewed the incidence and severity of dermatologic toxicities associated with ibrutinib therapy. The analysis revealed that ibrutinib is associated with various dermatologic adverse events, emphasizing the importance for clinicians to be familiar with them for proper management and improved patient outcomes.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2022)
Review
Hematology
Emma Leitinger, Zane Kaplan
Summary: Autoreactive B-cells play a crucial role in the development of autoimmune disorders, and therapies targeting these cells, such as BTK inhibitors, have shown promise in treating autoimmune haematologic conditions.
TRANSFUSION MEDICINE REVIEWS
(2022)
Review
Pharmacology & Pharmacy
Kinga Krawczyk, Katarzyna Sladowska, Przemyslaw Holko, Pawel Kawalec
Summary: This study aimed to compare the safety profile of tyrosine kinase inhibitors (TKIs) used as monotherapy or combination therapy for the first-line treatment of metastatic clear cell RCC. The results showed that sorafenib and tivozanib used as monotherapy were the best treatment options, while the safety profile was poorer when TKIs were used in combination with immunological agents.
FRONTIERS IN PHARMACOLOGY
(2023)