Differential synergistic effects of palbociclib and doxorubicin on doxorubicin-resistant cancer cells with diverse tumor origins.

Palbociclib is a dual inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6). Palbociclib has frequently been studied in breast cancer cells and has also been linked to function of P-glycoprotein (P-gp), main protein responsible for cancer drug resistance. However, the effect of Palbociclib on cancer drug resistance and specifically doxorubicin-resistant cells overexpressing P-gp have limitedly been studied in the literature.

Investigation of evolutionary dynamics for drug resistance in 3D spheroid model system using cellular barcoding technology.

Complex evolutionary dynamics governing the drug resistance is one of the major challenges in cancer treatment. Understanding these mechanisms requires a sequencing technology with higher resolution to delineate whether pre-existing or de novo drug mechanisms are behind the drug resistance. Combining this technology with clinically very relevant model system, namely 3D spheroids, better mimicking tumorigenesis and drug resistance have so far been lacking.

Systems Biology and Experimental Model Systems of Cancer.

Over the past decade, we have witnessed an increasing number of large-scale studies that have provided multi-omics data by high-throughput sequencing approaches. This has particularly helped with identifying key (epi)genetic alterations in cancers. Importantly, aberrations that lead to the activation of signaling networks through the disruption of normal cellular homeostasis is seen both in cancer cells and also in the neighboring tumor microenvironment.

15-LOX-1 has diverse roles in the resensitization of resistant cancer cell lines to doxorubicin.

Lipoxygenases (LOXs) are a family of enzymes that can oxygenate polyunsaturated fatty acids. As a member of the family, 15-lipoxygenase-1 (15-LOX-1) specifically metabolizes arachidonic acid and linoleic acid. 15-LOX-1 can affect physiological and pathophysiological events via regulation of the protein-lipid interactome, alterations in intracellular redox state and production of lipid metabolites that are involved in the induction and resolution of inflammation.