Due to the widespread use of tyrosine kinase inhibitors (TKIs), which have largely supplanted cytotoxic chemotherapy as the first-line therapeutic choice for patients with advanced non-small cell lung cancer (NSCLC) who have oncogene driver mutations, advanced NSCLC patients with oncogene driver mutations had much long median survival. However, TKIs' long-term efficacy is harmed by resistance to them. TKIs proved to have a limited potential to permeate cerebrospinal fluid (CSF) as well. Only a small percentage of plasma levels could be found in CSF at usual doses. Therefore, TKIs monotherapy may have a limited efficacy in individuals with brain metastases. Radiation has been demonstrated to reduce TKIs resistance and disrupt the blood-brain barrier (BBB). Previous trials have shown that local irradiation for bone metastases might improve symptoms, in addition, continuous administration of TKIs combined with radiotherapy was linked with beneficial progression-free survival (PFS) and overall survival (OS) for oligometastasis or bone metastasis NSCLC with oncogene driver mutations. The above implied that radiotherapy combined with targeted therapy may have a synergistic impact in patients with advanced oncogene driver-mutated NSCLC. The objective of this article is to discuss the value of radiotherapy in the treatment of those specific individuals.
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http://dx.doi.org/10.3389/fonc.2022.863715 | DOI Listing |
Discov Oncol
January 2025
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.
Monotherapy with anti-programmed cell death protein 1 (PD-1) monoclonal antibody has been approved for the treatment of advanced non-small cell lung cancer with positive programmed cell death-ligand 1 (PD-L1) expression and oncogene wild type, which revealed survival benefit compared with chemotherapy. Nevertheless, certain patients develop rapid progression on anti-PD-1 inhibitor monotherapy. This novel pattern is called hyperprogressive disease (HPD), and the underlying mechanism and molecular characteristics still leaves not clear.
View Article and Find Full Text PDFTher Adv Med Oncol
January 2025
Department of General Surgery, The First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, Jiangsu 215006, China.
Despite the availability of multiple treatment options for breast cancer, challenges such as adverse events, drug resistance, and disease progression persist for patients. The identification of human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers, alongside the development of HER2-targeted therapies, has significantly improved the prognosis of HER2-amplified breast cancers. However, therapeutic options remain limited for HER2-overexpressing or HER2-negative breast cancers.
View Article and Find Full Text PDFNPJ Precis Oncol
January 2025
Zentalis Pharmaceuticals, Inc., San Diego, CA, USA.
Upregulation of Cyclin E1 and subsequent activation of CDK2 accelerates cell cycle progression from G1 to S phase and is a common oncogenic driver in gynecological malignancies. WEE1 kinase counteracts the effects of Cyclin E1/CDK2 activation by regulating multiple cell cycle checkpoints. Here we characterized the relationship between Cyclin E1/CDK2 activation and sensitivity to the selective WEE1 inhibitor azenosertib.
View Article and Find Full Text PDFESMO Open
January 2025
Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address:
Background: In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.
Materials And Methods: Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment.
Am J Med Genet C Semin Med Genet
January 2025
Gastrointestinal and Endocrine Tumor Unit, Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona, Spain.
RET gene is a driver of thyroid cancer (TC) tumorigenesis. The incidence of TC has increased worldwide in the last few decades, both in medullary and follicular-derived subtypes. Several drugs, including multikinase and selective inhibitors, have been explored.
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