Background: Selective Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of breast cancer and have potential in other cancers, being manageable drugs yet with some bone marrow toxicity. Selective CDK9 inhibitors (CDK9i) never advanced into clinical use, partly due to side effects, including gastrointestinal toxicity, and a small window between activity and cytotoxicity, which results in a narrow therapeutic index (TI).
Methods: To overcome the drawbacks of CDK4/6 and CDK9 inhibitors, we have developed myrtleciclib, a selective CDK4/6/9 inhibitor with few non-critical molecular off-targets.
The Italian Interministerial Decree of February 11, 2021, introduces the diesel engine exhaust (DDE) among the carcinogenic occupational compounds, also establishing an occupational exposure limit. Elemental carbon (EC), improperly called black carbon, has been proposed as a tracer of DDE exposure; EC is the carbon that is quantified in the ambient matrixes after all the organic carbon has been removed; traditionally, EC is measured with a thermo-optical analytical technique. EC determination and relative interpretation are challenging for the following reasons: (i) the scarce availability of equipped laboratories hampers EC analysis, (ii) EC interpretation is not easy due to the lack of reference values.
View Article and Find Full Text PDFPatients with cancer of unknown primary (CUP) carry the double burden of an aggressive disease and reduced access to therapies. Experimental models are pivotal for CUP biology investigation and drug testing. We derived two CUP cell lines (CUP#55 and #96) and corresponding patient-derived xenografts (PDXs), from ascites tumor cells.
View Article and Find Full Text PDFThe approval of immune checkpoint inhibitors (ICIs) has revolutionized the management of metastatic renal cell carcinoma (RCC), introducing several ICI-based combinations as the new standard of care for affected patients. Nonetheless, monotherapy with antiangiogenic tyrosine kinase inhibitors (TKIs), such as pazopanib or sunitinib, still represents a first-line treatment option for selected patients belonging to the favorable risk group according to the International mRCC Database Consortium (IMDC) model. After TKI monotherapy, the main second-line option is represented by ICI monotherapy with the anti-Programmed Death Receptor 1(PD-1) nivolumab.
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