RESUMO
m6A (N6-methyladenosine) methylation, a well-known modification in tumour epigenetics, dynamically and reversibly fine tunes the entire process of RNA metabolism. Aberrant levels of m6A and its regulators, which can predict the survival and outcomes of cancer patients, are involved in tumorigenesis, metastasis and resistance. Ovarian cancer (OC) ranks first among gynaecological tumours in the causes of death. At first diagnosis, patients with OC are usually at advanced stages owing to a lack of early biomarkers and effective targets. After treatment, patients with OC often develop drug resistance. This article reviews the recent experimental advances in understanding the role of m6A modification in OC, raising the possibility to treat m6A modification and its regulators as promising diagnostic markers and therapeutic targets for OC.
RESUMO
Abnormal activation of the cyclin-dependent kinases (CDKs), which result in aberrant cell proliferation, is one of the inherent characteristics of tumor. Thus targeting the activity of CDKs represents a promising tumor therapeutic strategy. Currently, the specific inhibitors that target CDK4 and CDK6 have been approved for the treatment of estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+ HER2-) breast cancer in combination with endocrine therapy; other combination strategies are being tested in a number of clinical trials. However, the acquired resistance to CDK4/6 inhibitors has emerged. As the cell cycle is orchestrated by a series of biological events, the alterations of other molecular events that regulate the cell cycle progression may be involved in intrinsic resistance to CDK4/6 inhibitors. In this review we mainly discuss the mechanisms underlying intrinsic resistance and acquired resistance to CDK4/6 inhibitors as well as combination strategies with other signal pathway inhibitors being tested in clinical and pre-clinical studies, to extend the use of CDK4/6 inhibitors in tumor treatment.