We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy.
- Authors
Kildey, Katrina; Gandhi, Neha S.; Sahin, Katherine B.; Shah, Esha T.; Boittier, Eric; Duijf, Pascal H. G.; Molloy, Christopher; Burgess, Joshua T.; Beard, Sam; Bolderson, Emma; Suraweera, Amila; Richard, Derek J.; O'Byrne, Kenneth J.; Adams, Mark N.
- Abstract
Platinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients. Kildey et al find that high levels of mitotic regulator CDCA3 correlates with sensitivity to platinum agents in non-small cell lung cancer patients and cell lines. They show that interfering with CDCA3 degradation through CK2 inhibition enhances CDCA3 levels and increases sensitivity to platinum agents suggesting a therapeutic route.
- Subjects
NON-small-cell lung carcinoma; CANCER chemotherapy; PLATINUM isotopes; IMMUNOTHERAPY; CELL cycle; CELL lines
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02136-8