Next-generation sequencing reveals mutations in RB1, CDK4 and TP53 that may promote chemo-resistance to palbociclib in ovarian cancer


Despite therapeutic advances, ovarian cancer (OC) remains the seventh most commonly diagnosed cancer and the eighth leading cause of cancer-related deaths among women [1]. Although the incidence and mortality of OC are high, effective detection and therapeutic management are still lacking [2]. The 5-year survival rate is about 95% if diagnosed and treated while the disease is confined to the ovary; however, unfortunately, only around 30% of OC cases are detected at early stages [3]. This highlights the importance of understanding the molecular pathogenesis of OC; thus, new drug targets and biomarkers that facilitate early detection can be identified. Although several risk factors have been identified, the etiology of OC is poorly understood and the genetic implication remains largely unaddressed [4]. While germline mutations in BRCA1 and BRCA2 are the most common genetic aberrations in familial forms of ovarian carcinomas; mutations in the two tumor suppressors, TP53 and RB1, are the most frequent alterations in sporadic OC [4]. This points to the importance of the interconnecting pathways that control both TP53 and RB1 in the etiology of cancer and subsequently in the development of refined targeted therapies [5]. In the current study, we aim to discuss the clinical and molecular profile of our patient diagnosed with OC and to align the genetic alterations with the acquired chemoresistance. On the other hand, we propose the underlying mechanism leading to chemo-resistance, which will assist in exploring molecular therapeutic strategies in this OC patient.


Said El Shamieh


Fatima Saleh, Shafika Assaad, Fadi Farhat

Journal/Conference Information

Drug Metabolism and Personalized Therapy,DOI: 10.1515/dmpt-2018-0027, ISSN: 2363-8915, Volume: 34, Issue: 2, Pages Range: 1-5,