Next-generation sequencing reveals mutations in RB1, CDK4 and TP53 that may promote chemo-resistance to palbociclib in ovarian cancer.
Said El ShamiehFatima SalehShafka AssaadFadi FarhatPublished in: Drug metabolism and personalized therapy (2019)
Because of the profound heterogeneity of ovarian cancer at the clinical, cellular and molecular levels, herein we discuss the molecular findings at the protein and genetic levels seen in our patient. Immunohistochemistry showed a complete loss of phosphatase and tensin homolog, this observation was the reason behind prescribing the CDK4/6 inhibitor palbociclib. However, there was no response to treatment. Next-generation sequencing analysis was performed showing a nonsense mutation, p.R552X in retinoblastoma 1 (RB1). This nonsense variation will possibly lead to a truncated protein lacking the domain responsible for interaction with E2F, an event that will induce cell cycle progression and, thus, be responsible for the chemo-resistance to palbociclib.
Keyphrases
- cell cycle
- cell proliferation
- copy number
- metastatic breast cancer
- photodynamic therapy
- combination therapy
- primary care
- protein protein
- cancer therapy
- circulating tumor
- case report
- single cell
- binding protein
- single molecule
- locally advanced
- genome wide
- intellectual disability
- small molecule
- emergency department
- autism spectrum disorder
- drug delivery
- protein kinase
- smoking cessation
- adverse drug