Oncogenic conversion of receptor protein tyrosine kinases (RTK) is a frequent feature of malignant cells. This knowledge has fostered efforts to develop target-specific low molecular weight therapeutics able to obstruct RTK signalling. The clinical efficacy of the ABL- and KIT-inhibitors are paradigmatic of the power of this approach. Here, we focus on small-molecule inhibitors for RTKs involved in human cancer. In particular, we examine the KIT, MET and RET receptors that are targeted by genetic alterations in both sporadic and familial human tumours.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/0929867054367266 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Monitoring neoadjuvant treatment-induced surgical benefit in GIST patients using CT-based radiological criteria.
Surg Open Sci
August 2024
Department of Surgical Oncology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
Objective: This single-centre retrospective study aims to determine the incidence of therapy-induced surgical benefit in patients with non-metastatic gastrointestinal stromal tumour (GIST) treated with neoadjuvant tyrosine kinase inhibitors (TKI) and evaluate whether this can be predicted by radiological response criteria.
Methods: Thirty-nine non-metastatic GIST patients were treated with neoadjuvant TKI treatment, followed by curative-intended surgery, and monitored using contrast-enhanced computed tomography (CE-CT). Surgical benefit was independently assessed by two surgical oncologists and was defined by de-escalation of surgical strategy or reduced surgical complexity.
Identification of sulfonylated indolo[1,2-]quinolines as EGFR tyrosine kinase inhibitors.
RSC Adv
January 2025
Department of Chemistry, Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University Rama VI Road Bangkok 10400 Thailand
Two series of indolo[1,2-]quinolines (IQs), comprising six 6-trifluoromethylthio indolo[1,2-]quinolines and nine 6-arenesulfonyl indolo[1,2-]quinolines, were screened for their inhibitory activity against EGFR tyrosine kinase (EGFR-TK) using the ADP-Glo™ kinase assay. Among the 15 IQs screened, four compounds exhibited cytotoxic activity against a lung cancer cell line (A549) that was as potent as the known drug afatinib with lower cytotoxicity in Vero cells. In addition, while they displayed cytotoxic activity against a head and neck squamous cell carcinoma cell line (SCC cells), they were inactive against a colorectal cancer cell line (LS174T cells).
View Article and Find Full Text PDFInfectious complications associated with immune and targeted anti-cancer therapies: a retrospective study of the FDA Adverse Events Reporting System (FAERS).
Expert Opin Drug Saf
January 2025
Department of Pharmacy Practice and Science, R Ken Coit College of Pharmacy, University of Arizona, Tucson, AZ, USA.
Background: Immune and targeted anti-cancer therapies are associated with an increased risk of infectious complications. The objectives of the present study were to evaluate the infectious complications associated with immune and targeted anti-cancer drugs.
Research Design And Methods: This was a retrospective for immune and targeted anti-cancer drugs submitted to the FDA Adverse Event Reporting System (FAERS) from 1996 to 20 March 2024.
Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia.
Acta Pharmacol Sin
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.
View Article and Find Full Text PDFProspective Investigation Unravels Plasma Proteomic Links to Dementia.
Mol Neurobiol
January 2025
Research and Innovation Center, Shanghai Pudong Hospital, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, 200433, China.
Investigating plasma proteomic signatures of dementia offers insights into its pathology, aids biomarker discovery, supports disease monitoring, and informs drug development. Here, we analyzed data from 48,367 UK Biobank participants with proteomic profiling. Using Cox and generalized linear models, we examined the longitudinal associations between proteomic signatures and dementia-related phenotypes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!