Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are the primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after the initial treatment. In the past two decades, immunotherapy has rapidly developed, and has revolutionized the treatment of various types of cancer. Despite the fact that immunotherapy response rates among ovarian cancer patients remain modest, treatment with immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- and TCR-engineered T cells is rapidly developing. Therapeutic efficiency could be improved significantly if immunotherapy is included as an adjuvant therapy, in combination with chemotherapy, radiation therapy, and the use of anti-angiogenesis drugs, and poly ADP ribose polymerase inhibitors (PARPi). Newly developed technologies that identify therapeutic targets, predict treatment efficacy, rapidly screen potential immunotherapy drugs, provide neoadjuvant immunotherapy, and utilize nanomedicine technology provide new opportunities for the treatment of ovarian cancer, and have the potential to prolong patient survival. However, important issues that may hinder the efficacy of such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, and toxicity of the treatments, including neurotoxicity, must be taken into account and addressed for these therapies to be effective.

BET proteins, which influence gene expression and contribute to the development of cancer, are epigenetic interpreters. Thus, BET inhibitors represent a novel form of epigenetic anticancer treatment. Although preliminary clinical trials have shown the anticancer potential of BET inhibitors, it appears that these drugs have limited effectiveness when used alone. Therefore, given the limited monotherapeutic activity of BET inhibitors, their use in combination with other drugs warrants attention, including the meaningful variations in pharmacodynamic activity among chosen drug combinations. In this paper, we review the function of BET proteins, the preclinical justification for BET protein targeting in cancer, recent advances in small-molecule BET inhibitors, and preliminary clinical trial findings. We elucidate BET inhibitor resistance mechanisms, shed light on the associated adverse events, investigate the potential of combining these inhibitors with diverse therapeutic agents, present a comprehensive compilation of synergistic treatments involving BET inhibitors, and provide an outlook on their future prospects as potent antitumor agents. We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy.

Ovarian cancer is the leading cause of death in gynecologic malignancies. Profiling of endogenous metabolites has potential to identify changes caused by cancer and provide inspiring insights into cancer metabolism. To systematically investigate ovarian cancer metabolism, we performed metabolic profiling of 448 plasma samples related to epithelial ovarian cancer (EOC) based on ultra‐performance liquid chromatography mass spectrometry in both positive and negative modes. These unbiased metabolomic profiles could well distinguish EOC from benign ovarian tumor (BOT) and uterine fibroid (UF). Fifty‐three metabolites were identified as specific biomarkers for EOC, and this is the first report of piperine, 3‐indolepropionic acid, 5‐hydroxyindoleacetaldehyde and hydroxyphenyllactate as metabolic biomarkers of EOC. The AUC values of these metabolites for discriminating EOC from BOT/UF and early‐stage EOC from BOT/UF were 0.9100/0.9428 and 0.8385/0.8624, respectively. Meanwhile, our metabolites were able to distinguish early‐stage EOC from late‐stage EOC with an AUC of 0.8801. Importantly, analysis of dysregulated metabolic pathways extends our current understanding of EOC metabolism. Metabolic pathways in EOC patients are mainly characterized by abnormal phospholipid metabolism, altered l‐tryptophan catabolism, aggressive fatty acid β‐oxidation and aberrant metabolism of piperidine derivatives. Together, these metabolic pathways provide a foundation to support cancer development and progression. In conclusion, our large‐scale plasma metabolomics study yielded fundamental insights into dysregulated metabolism in ovarian cancer, which could facilitate clinical diagnosis, therapy, prognosis and shed new lights on ovarian cancer pathogenesis.

Cervical cancer (CC) still remains a common and deadly malignancy among females in developing countries. More accurate and reliable diagnostic methods/biomarkers should be discovered. In this study, we performed a comprehensive analysis of metabolomics (285 samples) and transcriptomics (52 samples) on the potential diagnostic implication and metabolic characteristic description in cervical cancer. Sixty-two metabolites were different between CC and normal controls (NOR), in which 5 metabolites (bilirubin, LysoPC(17:0), n-oleoyl threonine, 12-hydroxydodecanoic acid and tetracosahexaenoic acid) were selected as candidate biomarkers for CC. The AUC value, sensitivity (SE), and specificity (SP) of these 5 biomarkers were 0.99, 0.98 and 0.99, respectively. We further analysed the genes in 7 significantly enriched pathways, of which 117 genes, that were expressed differentially, were mainly involved in catalytic activity. Finally, a fully connected network of metabolites and genes in these pathways was built, which can increase the credibility of our selected metabolites. In conclusion, our biomarkers from metabolomics could set a path for CC diagnosis and screening. Our results also showed that variables of both transcriptomics and metabolomics were associated with CC.