Tyrosine kinase inhibitors revolutionized cancer therapy but still evoke strong adverse effects that can dramatically reduce patients’ quality of life. One possibility to enhance drug safety is the exploitation of prodrug strategies to selectiv...
We have developed a highly sensitive promoter trap vector system using transposons to generate reporter cells with high efficiency. Using an EGFP/luciferase reporter cell clone responsive to forskolin, which is thought to activate adenylate cyclase,...
Tyrosine kinase inhibitor (TKI) therapy is gaining attraction in advanced cancer therapeutics due to the ubiquity of kinases in cell survival and differentiation. Great progress was made in the past years in identifying tyrosine kinases that can func...
In cases in which a rapid metabolism is the cause of an unfavorable pharmacokinetic profile, it is important to determine the Sites of Metabolism (SoMs) of a molecule to introduce the necessary modifications to improve the stability of the compound....
Chronic myeloid leukemia (CML) is characterized by the presence of the BCR-ABL1 fusion gene, which encodes a constitutive active tyrosine kinase considered to be the pathogenic driver capable of initiating and maintaining the disease. Despite the rem...
Sunitinib (Su) is a tyrosine kinase inhibitor with antiangiogenic and antineoplastic effects that is recommended therapy for renal cell carcinoma, gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. Arterial hypertension is one of...
Triple-negative breast cancer (TNBC) is associated with a poor prognosis and the absence of targeted therapy. c-Kit, a receptor tyrosine kinase (RTK), is considered a molecular target for anticancer drugs. Tyrosine kinase inhibitors (TKIs) recognizin...
Background and Clinical Significance: Chronic Myeloid Leukemia (CML) management has been revolutionized by tyrosine kinase inhibitors (TKIs), though cardiovascular and thrombotic complications remain a concern, especially in patients with underlying...
Cancer remains a major global health burden driven by complex biological mechanisms, and while targeted therapies like tyrosine kinase inhibitors (TKIs) have revolutionized treatment, their efficacy and safety are significantly influenced by drug&nda...
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm constituting approximately 15% of newly diagnosed leukemia in adult patients. Development of tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes in patients with chroni...
Vascular endothelial growth factor A (VEGFA) and its receptor VEGFR2 are the main targets of antiangiogenic therapies, and proteinuria is one of the common adverse events associated with the inhibition of the VEGFA/VEGFR2 pathway. The proteinuric kid...
Tyrosine kinase inhibitors (TKIs) are currently the standard chemotherapeutic agents for the treatment of chronic myeloid leukemia (CML). However, due to TKI resistance acquisition in CML patients, identification of new vulnerabilities is urgently re...
Tyrosine kinase inhibitors (TKIs) have been extensively used as a treatment for chronic myeloid leukemia (CML). Dasatinib is a broad-spectrum TKI with off-target effects that give it an immunomodulatory capacity resulting in increased innate immune r...
Non-small cell lung cancer (NSCLC) is a complex disease often driven by activating mutations or amplification of the epidermal growth factor receptor (EGFR) gene, which expresses a transmembrane receptor tyrosine kinase. Targeted anti-EGFR treatments...
Tyrosine kinase inhibitors (TKIs) are the first-line therapy for non-small-cell lung cancers (NSCLC) that harbour sensitising mutations within the epidermal growth factor receptor (EGFR). However, resistance remains a key issue, with tumour relapse l...
Abl1 kinase has important biological roles. The Bcr-Abl1 fusion protein creates undesired kinase activity and is pathogenic in 95% of chronic myeloid leukemia (CML) and 30% of acute lymphoblastic leukemia (ALL) patients. Targeted therapies to these d...
(1) Background: We aimed to evaluate the risk of hepatitis B virus (HBV) reactivation in lung cancer patients treated with tyrosine kinase inhibitor (TKI), particularly in those with resolved HBV infection. (2) Methods: In this retrospective hospital...
Activating double mutations L858R/T790M in the epidermal growth factor receptor (EGFR) region are often observed as the cause of resistance to tyrosine kinase inhibitors (TKIs). Third-generation EGFR-TKIs, such as osimertinib and rociletinib (CO-1686...
We evaluated the efficacy and safety of combination therapy with immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKI) as first-line therapy for patients diagnosed as having advanced or metastatic renal cell carcinoma (mRCC). We en...
Limiting bone resorption and regenerating bone tissue are treatment goals in myeloma bone disease (MMBD). Physical stimuli such as mechanical loading prevent bone destruction and enhance bone mass in the MOPC315.BM.Luc model of MMBD. It is unknown wh...
The development of resistance to tyrosine kinase inhibitors (TKIs) is a major cause of treatment failure in metastatic renal cell carcinoma (mRCC). A deeper understanding of the metabolic mechanisms associated with TKI resistance is critical for refi...
Tyrosine kinase inhibitors (TKI) have revolutionised the treatment of CML. However, TKI do not eliminate the leukaemia stem cells (LSC), which can re-initiate the disease. Thus, finding new therapeutic targets in CML LSC is key to finding a curative...
Tyrosine kinase inhibitors are a new class of anticancer drugs, that are capable of directly interacting with the catalytic site of the target enzyme and thereby inhibiting catalysis. Therapeutically useful tyrosine kinase inhibitors are not specific...
Herein, the in vitro metabolism of tyrosine kinase inhibitor cabozantinib, the drug used for the treatment of metastatic medullary thyroid cancer and advanced renal cell carcinoma, was studied using hepatic microsomal samples of different human donor...
For chronic myeloid leukemia (CML) patients with a known risk of cardiovascular events (CVE), imatinib is often recommended for first-line tyrosine kinase inhibitor (TKI) treatment rather than a second-generation TKI (2G-TKI) such as nilotinib or das...
Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate comprising trastuzumab linked to a payload DXd, has been extensively used to treat various cancers harboring HER2 overexpression. However, resistance development has been a major challe...
We performed a systematic review and meta-analysis to assess the efficacy of EGFR-tyrosine kinase inhibitors (TKI) retreatment in advanced/metastatic non-small-cell lung cancer (NSCLC) patients. We systematically searched PubMed, Embase, Cochrane dat...
(1) Background: We performed a meta-analysis to examine whether combined epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) and immune checkpoint inhibitor (ICI) increases treatment-related adverse events (trAEs) in advanced non-small cell...
Background: A major issue in Chronic Myeloid Leukemia (CML) is the persistence of quiescent leukemia stem cells (LSCs) in the hematopoietic niche under tyrosine kinase inhibitor (TKI) treatment. Results: Here, using CFSE sorting, we show that low-pro...
Tyrosine kinase inhibitors are a rapidly expanding class of molecular targeted therapies for the treatment of various types of cancer and other diseases. An increasing number of clinically important small molecule tyrosine kinase inhibitors have been...
Conventional cytotoxic chemotherapy involving DNA-interacting agents and indiscriminate cell death is no longer the future of cancer management. While chemotherapy is not likely to completely disappear from the armamentarium; the use of targeted ther...
Background and Objectives: Systemic conversion of stage III–IV non-small-cell lung cancer (NSCLC) to a surgically resectable state with immune checkpoint inhibitors (ICIs) or tyrosine kinase inhibitors (TKIs) creates an emerging cohort of candi...
Combined inhibition of vascular endothelial growth factor receptor (VEGFR) and the programmed cell death protein 1 (PD-1) pathways has shown efficacy in multiple cancers; however, the clinical outcomes show limited benefits and the unmet clinical nee...
In a scenario characterized by continuous improvement in outcomes, Philadelphia chromosome-positive (Ph+) ALL, once considered a biologically defined subtype with one of the poorest prognoses, now includes patients achieving long-term survival even w...
Background/Objectives: Tyrosine kinase inhibitors (TKIs) have transformed the treatment of chronic myeloid leukemia (CML), yet emerging evidence indicates an increased risk of vascular adverse events, particularly peripheral artery disease (PAD). Rel...
Bladder cancer is a common malignancy associated with high recurrence rates and potential progression to invasive forms. Sorafenib, a multi-targeted tyrosine kinase inhibitor, has shown promise in anti-cancer therapy, but its cytotoxicity to normal c...
Dysregulational EGFR, KRAS, and mTOR pathways cause metabolic reprogramming, leading to progression of gastric cancer. Afatinib (Afa) is a broad-spectrum tyrosine kinase inhibitor that reduces cancer growth by blocking the EGFR family. MicroRNA 125 (...
Receptor tyrosine kinases are critical for the growth and proliferation of many different cancers and therefore represent a potential vulnerability that can be therapeutically exploited with small molecule inhibitors. Over forty small molecule inhibi...
We presented an approach to address cancer cell chemotaxis and response to tyrosine kinase inhibitor PD153035 at the single-cell level. We applied an optical tweezer system together with the platform at the single-cell level to manipulate an epiderma...
Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However,...
Tyrosine kinase inhibitor (TKI) drugs have significantly improved chronic myeloid leukemia (CML) outcomes. Neopeptides from CML cells may induce specific immune responses, which are crucial for deep molecular (DMR) and treatment-free remission (TFR)....
Glioblastoma (GBM) is the most common and lethal form of malignant brain tumor. GBM patients normally undergo surgery plus adjuvant radiotherapy followed by chemotherapy. Numerous studies into the molecular events driving GBM highlight the central ro...
The fundamental pathophysiology of malignancies is dysregulation of the signalling pathways. Protein tyrosine kinases (PTKs) are among the enzymes which, if mutated, play a critical role in carcinogenesis. The best-studied rearrangement, which enhanc...
Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new ef...
Ovarian cancer is one of the most lethal gynaecological malignancies worldwide. Despite high success rates following first time treatment, this heterogenous disease is prone to recurrence. Oncogenic activity of receptor tyrosine kinases is believed t...
Tyrosine kinase inhibitors are a class of chemotherapeutic drugs that target specific protein kinases. These tyrosine kinase inhibitors constitute a relatively new class of drugs which target for instance Bcr-Abl, Epidermal Growth Factor Receptor (EG...
Imatinib mesylate, a selective inhibitor of tyrosine kinases, has excellent efficacy in the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST). Inducing durable responses and achieving prolonged survival, it has b...
Background: ABL1 tyrosine kinase inhibitor discontinuation securely became among the therapeutic goal for chronic myeloid leukemia chronic phase patients (CML-CP). To establish successful prognostic factors for treatment-free remission (TFR), it is n...
Background: Unlike cytotoxic agents, novel antineoplastic drugs can variably affect thyroid function and so impair patient outcomes. However, the widely used standard thyroid tests have demonstrated low sensitivity for detecting early thyroid damage...
Background: Although tyrosine kinase inhibitors (TKIs) are still recommended as the standard therapy in renal cell carcinoma (RCC), the high frequency of adverse events is a weakness of this therapy. Because royal jelly (RJ) possesses anti-inflammato...
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