Customer Publication
The search for CDK4/6 inhibitor biomarkers has been hampered by inappropriate proliferation assays
Journal: npj Breast Cancer (2024)
Institution: Cellular and Systems Medicine, Jacqui Wood Cancer Centre, School of Medicine, University of Dundee, Dundee, UK
Research Areas: Cancer Research
Cell Lines: hTERT-RPE1 (RPE1), MCF7, T47D, H1299, MCF10A, MDA-MB-231, Jurkat (clone E6-1), HH cells, SKOV3, DLD1-FRT, KARPAS-299 (The human ovarian adenocarcinoma SKOV3. The human colorectal cancer line DLD1-FRT. The human non-Hodgkins Ki-positive large cell lymphoma KARPAS-299.)
Summary: CDK4/6 inhibitors are effective at treating advanced HR+ /HER2- breast cancer, however biomarkers that can predict response are urgently needed. Using a wide range of cell types, this study demonstrated that previous large-scale screens designed to identify which tumour types or genotypes are most sensitive to CDK4/6 inhibitors have misrepresented the responsive cell lines because of a reliance on metabolic proliferation assays such as MTT or ATP assays. Even if cell proliferation is arrested, cell size may increase, resulting in more active mitochondria and higher values in e.g. MTT assays. CDK4/6 inhibitors and any other anti-cancer drugs that arrest the cell cycle but permit continued cell growth, must now be re-screened against a wide range of cell types using an appropriate proliferation assay. HoloMonitor was used to confirm actual lengths of cell cycle, to compare with results from metabolic assays.