healthcare Article The Role of CDK4 in the Pathogenesis of Pancreatic Cancer Emily Jiggens 1 , Maria Mortoglou 1 , Guy H. Grant 2 and Pinar Uysal-Onganer 1, *   Citation: Jiggens, E.; Mortoglou, M.; Grant, G.H.; Uysal-Onganer, P. The Role of CDK4 in the Pathogenesis of Pancreatic Cancer. Healthcare 2021, 9, 1478. https://doi.org/10.3390/ healthcare9111478 Academic Editors: Nur Mohammad Hassan, Rahena Akhter and Paolo Cotogni Received: 20 August 2021 Accepted: 28 October 2021 Published: 30 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Cancer Research Group, School of Life Sciences, University of Westminster, London W1W 6UW, UK; w1712684@my.westminster.ac.uk (E.J.); w1754188@my.westminster.ac.uk (M.M.) 2 Department of Life Sciences, University of Bedfordshire, Park Square, Luton LU1 3JU, UK; guy.grant@beds.ac.uk * Correspondence: p.onganer@westminster.ac.uk; Tel.: +44-(0)207-911-5151 (ext. 64581) Abstract: Pancreatic cancer (PC) continues to have the lowest overall survival and the lack of effective early diagnosis. Cyclin-dependent kinase 4 (CDK4) plays a fundamental role in the orderly progression of the cell cycle, binding to cyclin D to promote the progression through the G1/2 transition. The inhibition of CDK4/6 has therefore gained substantial interest in the hope of new and effective therapeutics in multiple cancers, such as advanced metastatic breast cancer. While the use of these agents is encouraging, their potential is yet to be fully explored. In this study we used the GLOBOCAN database to understand the most recent epidemiology of PC, Human Protein Atlas and KEGG to highlight the role, prevalence, and significance on patient survival of CDK4 in PC. We found that CDK4 cannot be used as prognostic in PC and no significant differences were observed between CDK4 expression and the patient’s clinical status, though larger studies, especially concerning CDK4 protein expressions, are required for a more thorough understanding. The use of CDK4/6 inhibitors in PC is still in clinical trials. However, due to only modest improvements observed in the use of single-agent therapies, efforts have focused on combinatorial approaches. Keywords: pancreatic cancer; CDK4; CDK4/6 inhibitor; epidemiology 1. Introduction Pancreatic Cancer (PC) is a highly aggressive malignancy, which continues to have the lowest overall 1- and 5-year patient survival rates amongst all cancer sites in the United Kingdom, at 25% and 7%, respectively [1]. While surgical resection remains the only curative treatment available, 80–85% of tumours are diagnosed at late and unresectable stages, with evidence of locally advanced or metastatic disease. For the small proportion of patients that do qualify for surgical care, survival rates are modest - despite numerous benefits observed when studying the early detection of PC [2] - and patients frequently suffer from local recurrence, metachronous metastasis and high tumour chemoresistance following resection, seen in up to 80% of cases [3]. Despite advances in diagnostic tech- nology, the high frequency of late-stage diagnoses, and the associated poor prognosis, is largely attributable to the non-specific early-stage symptoms, the lack of specific and sensitive biomarkers, and the retroperitoneal position of the pancreas that restricts the accessibility of routine checks [4]. Pancreatic ductal adenocarcinoma (PDAC) is an invasive pancreatic epithelial neo- plasm with glandular differentiation and is the most prevalent histological subtype of PC, accounting for approximately 85% of pancreatic tumours; the terms PC and PDAC are often used synonymously. In recent studies, several subtypes of PDAC have been defined following gene expression analysis. The implications they hold for future precision medicine and targeted patient clinical care is promising: results show that the presence of stromal infiltration improves survival in patients with desmoplastic or stroma-activated subtypes, whereas basal-like tumours have an unfavourable prognosis and a poor median overall survival (OS) rate of 10.3 months. However, these lack consensus and a universally agreed classification system is required for implementation into routine clinical practice [5]. Healthcare 2021, 9, 1478. https://doi.org/10.3390/healthcare9111478 https://www.mdpi.com/journal/healthcare