Patients with advanced thyroid cancer, including advanced papillary thyroid cancer and anaplastic thyroid cancer (ATC), have low survival rates because of the lack of efficient therapies available that can combat their aggressiveness. A total of 90% of thyroid cancers have identifiable driver mutations, which often are components of the MAPK pathway, including , , and -fusions. In addition, Src is a non-receptor tyrosine kinase that is overexpressed and activated in thyroid cancer, which we and others have shown is a clinically relevant target. We have previously demonstrated that combined inhibition of Src with dasatinib and the MAPK pathway with trametinib synergistically inhibits growth and induces apoptosis in and -mutant thyroid cancer cells. Herein, we identified the pro-apoptotic protein BCL2L11 (BIM) as being a key mediator of sensitivity in response to combined dasatinib and trametinib treatment. Specifically, cells that are sensitive to combined dasatinib and trametinib treatment have inhibition of FAK/Src, MEK/ERK, and AKT, resulting in the dramatic upregulation of BIM, while cells that are resistant lack inhibition of AKT and have a dampened induction of BIM. Inhibition of AKT directly sensitizes resistant cells to combined dasatinib and trametinib but will not be clinically feasible. Importantly, targeting BCL-XL with the BH3-mimeitc ABT-263 is sufficient to overcome lack of BIM induction and sensitize resistant cells to combined dasatinib and trametinib treatment. This study provides evidence that combined Src and MEK1/2 inhibition is a promising therapeutic option for patients with advanced thyroid cancer and identifies BIM induction as a potential biomarker of response.
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http://dx.doi.org/10.3390/cancers15020378 | DOI Listing |
Endocrine
January 2025
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Purpose: To evaluate the diagnostic value of different subtypes of non-punctate echogenic foci in thyroid malignancy.
Methods: Retrospective research of 342 thyroid nodules with calcification was performed. The echogenic foci were divided into punctate echogenic foci (type I) and non-punctate echogenic foci (type II), and type II were further divided into four subtypes: macrocalcification (type IIa), continuous peripheral calcification (type IIb), discontinuous peripheral calcification (type IIc) and isolated calcification (type IId).
Funct Integr Genomics
January 2025
Institute of Infectious Diseases, Guangdong Province, Guangzhou Eighth People's Hospital, Guangzhou Medical University, 8 Huaying Road, Baiyun District, Guangzhou, 510440, China.
Hepatocellular carcinoma (HCC) remains a malignant and life-threatening tumor with an extremely poor prognosis, posing a significant global health challenge. Despite the continuous emergence of novel therapeutic agents, patients exhibit substantial heterogeneity in their responses to anti-tumor drugs and overall prognosis. The pentose phosphate pathway (PPP) is highly activated in various tumor cells and plays a pivotal role in tumor metabolic reprogramming.
View Article and Find Full Text PDFClin Exp Med
January 2025
Pathology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Lung cancer is one of the major causes of cancer morbidity and mortality. Subtyping of non-small cell lung cancer is necessary owing to different treatment options. This study is to evaluate the value of immunohistochemical expression of glypican-1 in the diagnosis of lung squamous cell carcinoma (SCC).
View Article and Find Full Text PDFDiagn Cytopathol
January 2025
Servizio di Endocrinologia e Diabetologia, Ente Ospedaliero Cantonale (EOC), Lugano, Switzerland.
The measurement of Calcitonin (Ctn) in fine-needle aspiration (FNA) washout fluids (FNA-Ctn) has demonstrated excellent sensitivity, significantly higher than FNA cytology, in detecting medullary thyroid carcinoma (MTC). However, the absence of a fixed cutoff value for FNA-Ctn poses a limitation. This study aimed to investigate whether the sensitivity of FNA-Ctn in detecting MTC varies with different cutoffs reported in the literature.
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