Humans ; Janus Kinase Inhibitors/therapeutic use* ; Vitiligo/drug therapy* ; Psoriasis ; Protein Kinase Inhibitors

Humans ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors

Zanubrutinib is a highly selective second-generation BTK inhibitor developed in China and first approved by the U.S. Food and Drug Administration (FDA) as a novel antineoplastic drug. In recent years, with the birth of molecularly targeted drugs, the treatment of B-cell lymphoma have entered the era of targeted therapy, and immunotherapy has been widely accepted. Especially in some relapsed and refractory lymphomas, zanubrutinib has shown deep and sustained remissions and a favorable safety, which lays a foundation for precision therapy. In this review the clinical application and new progress for zanubrutinib in B-cell lymphoma was summarized briefly.
Humans ; Lymphoma, B-Cell/drug therapy* ; Piperidines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Pyrazoles/therapeutic use* ; Pyrimidines/therapeutic use*

The development and progression of most cancers have been well recognized as the result of highly activated cell cycle. Cyclin dependent kinase 4/6 plays important roles not only in mitosis, but also in multiple biological processes that contribute to cancer development, such as aging, apoptosis and histone modification. Three FDA approved CDK4/6 inhibitors, Palbociclib, Ribociclib and Abemaciclib, have been used as targeted cancer therapeutic agents to benefit patients with endocrine therapy-resistant breast cancer and other types of cancer, prolonging their survival. However, the clinical application of these inhibitors also leads to acquired drug resistance and other problems. This paper reviews the regulatory roles of CDK4/6, the application of CDK4/6 inhibitors in cancer and the challenge of drug resistance.
Breast Neoplasms ; Cyclin-Dependent Kinase 4/therapeutic use* ; Cyclin-Dependent Kinase 6/therapeutic use* ; Female ; Humans ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use* ; Signal Transduction

Carcinoma, Non-Small-Cell Lung/drug therapy* ; Humans ; Immune Checkpoint Inhibitors ; Lung Neoplasms/drug therapy* ; Mitogen-Activated Protein Kinase Kinases/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Advanced prostate cancer, especially at the castration-resistant stage, remains incurable clinically and, therefore, urgently requires new therapeutics for the patients. PI3K is a family of critical cell signal transduction molecules and their over-activation is an important factor in cancer development and progression. It has been demonstrated that class IA PI3K p110 is drastically overexpressed in prostate cancer and involved in androgen receptor-mediated gene expression and castration-resistant progression and regarded as a potential therapeutic target for prostate cancer. Several p110-specific inhibitors have been reported recently and two of them, GSK2636771 and AZD8186, are being tested in clinical trials.
Aniline Compounds ; therapeutic use ; Chromones ; therapeutic use ; Humans ; Imidazoles ; therapeutic use ; Male ; Morpholines ; therapeutic use ; Neoplasm Proteins ; antagonists & inhibitors ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Prostatic Neoplasms, Castration-Resistant ; drug therapy ; enzymology ; Protein Kinase Inhibitors ; therapeutic use

OBJECTIVE: To explore the efficacy of tyrosine kinase inhibitor (TKI) combined with decitabine, homoharringtonine, and interferon regimen as maintenance therapy for blast phase chronic myeloid leukemia (CML-BP). METHODS: The clinical data of CML-BP patients who received the first major hematological response after induction therapy at The Affiliated Cancer Hospital of Zhengzhou University from June 2015 to December 2021 were analyzed retrospectively. The event-free survival, duration of remission, and overall survival of patients in TKI combined with decitabine, homoharringtonine, interferon group(n=18) and TKI combined with conventional chemotherapy group(n=10) were compared by log-rank test. RESULTS: A total of 28 patients were included, with a median age of 46 (24-58) years old. Kaplan-Meier survival analysis showed that patients in TKI combined with decitabine, homoharringtonine, interferon group had longer event-free survival (7.4 vs 4.3 months, P=0.043, HR＝0.44, 95% CI: 0.17-1.14), duration of overall remission (16.1 vs 6.6 months, P=0.005, HR＝0.32, 95% CI: 0.11-0.89), overall survival (34.3 vs 13.5 months, P=0.006, HR＝0.29, 95% CI: 0.10-0.82) compared with patients in TKI combined with conventional chemotherapy group. CONCLUSION The TKI combined with decitabine, homoharringtonine and interferon regimen can significantly prolong the survival of CML-BP patients who obtained the major hematological response compared with TKI combined with conventional chemotherapy regimen.
Humans ; Middle Aged ; Blast Crisis/drug therapy* ; Homoharringtonine/therapeutic use* ; Decitabine/therapeutic use* ; Interferons/therapeutic use* ; Tyrosine Protein Kinase Inhibitors ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use* ; Treatment Outcome

Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; Protein-Tyrosine Kinases ; antagonists & inhibitors

OBJECTIVELeukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment.

DATA SOURCESWe searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML. Clinical trial information was obtained from ClinicalTrials.gov. For the major purpose of this review that is to outline the latest therapeutic development of AML, we only listed the ongoing clinical trials for reference. However, the published results of complete clinical trials were also mentioned.

STUDY SELECTIONThis article reviewed the latest developments related to the diagnosis and treatment of AML. In the first portion, we provided some novel insights on the molecular basis of AML, as well as provided an update on the classification of AML. In the second portion, we summarized the results of research on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/Fms-like tyrosine kinase 3 (FLT3) inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. We will also highlight ongoing research and clinical trials in pediatric AML.

RESULTSWe described clonal evolution and how it changes our view on leukemogenesis, treatment responses, and disease relapse. Pediatric-specific genomic mapping was discussed with a novel diagnostic method highlighted. In the later portion of this review, we summarized the researches on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/FLT3 inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents.

CONCLUSIONGene sequencing techniques should set the basis for next-generation diagnostic methods of AML, and target therapy should be the focus of future clinical research in the exploration of therapeutic possibilities.

Antibodies, Monoclonal ; therapeutic use ; Humans ; Leukemia, Myeloid, Acute ; diagnosis ; drug therapy ; Protein Kinase Inhibitors ; therapeutic use ; fms-Like Tyrosine Kinase 3 ; antagonists & inhibitors

Objective: To investigate the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKi) ibrutinib or zanubrutinib monotherapy in newly diagnosed patients with Waldenström macroglobulinemia (WM) . Methods: The efficacy and adverse effects of 58 patients with newly diagnosed WM receiving BTKi monotherapy in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were analyzed retrospectively from January 2018 to August 2022. Results: The response of 55 patients may be examined. Forty patients received ibrutinib monotherapy for a median of 15 months, with an overall response rate (ORR) of 85%, a main remission rate (MRR) of 70%, and a very good partial remission (VGPR) rate of 10%. Fifteen patients received zanubrutinib monotherapy for a median of 13 months, with an ORR of 93%, an MRR of 73%, and a VGPR rate of 0%. For various reasons, 10 patients were converted from ibrutinib to zanubrutinib. Ibrutinib treatment lasted an average of 7.5 months before conversion. The median duration of zanubrutinib therapy after conversion was 3.5 months. The ORRs before and after conversion were 90% and 100%, MRRs were 80% and 80%, and VGPR rates were 10% and 50%, respectively. After a median of 16 months, the 24-month progression-free survival (PFS) rate of patients who received both BTKi was 86%. PFS did not differ statistically across individuals with low, medium, and high-risk ISS scores (P=0.998). All of the patients survived. The most common side effects of BTKi were neutropenia and thrombocytopenia, which occurred in 12% and 10% of all patients, respectively. Ibrutinib accounts for 5% of atrial fibrillation, and zanubrutinib has a 7% risk of bleeding. Conclusions: In treating WM, ibrutinib or zanubrutinib provides good efficacy and tolerable adverse effects.
Humans ; China ; Retrospective Studies ; Treatment Outcome ; Tyrosine Protein Kinase Inhibitors/therapeutic use* ; Waldenstrom Macroglobulinemia/drug therapy*