Metastatic castration-resistant prostate cancer (mCRPC) remains a terminal diagnosis with an aggressive disease course despite currently approved therapeutics. The recent successful development of poly ADP-ribose polymerase (PARP) inhibitors for patients with mCRPC and mutations in DNA damage repair genes has added to the treatment armamentarium and improved personalized treatments for prostate cancer. Other promising therapeutic agents currently in clinical development include the radiotherapeutic 177-lutetium-prostate-specific membrane antigen (PSMA)-617 targeting PSMA-expressing prostate cancer and combinations of immunotherapy with currently effective treatment options for prostate cancer. Herein, we have highlighted the progress in systemic treatments for mCRPC and the promising agents currently in ongoing clinical trials.
Esophageal cancer (EC) and gastric cancer (GC) often have an unfavorable prognosis. Therefore, research is being conducted to identify the molecular mechanisms underlying the tumorigenesis and progression of GC and EC, and to indicate novel therapeutic targets and clinically applicable biomarkers. The dysregulations and roles of long non-coding RNAs (lncRNAs) have been widely reported, and current published literature has shown that lncRNAs play important regulatory roles in the carcinogenesis and progression of EC and GC. The lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been investigated in a number of studies with regard to its pathogenic pathways and association with the prognosis of gastric and esophageal malignancies. As literature on the topic of MALAT1 in EC and GC continues to emerge, the present review aims to summarize all current knowledge on the association between MALAT1 expression and esophagogastric malignancies and to describe the pathogenic pathways and possible prognostic role of MALAT1 in esophagogastric cancer. As research studies on MALAT1 pathways in esophagogastric malignancies are ongoing, new possibilities for the diagnosis, prognosis and therapy of GC and EC are likely to be identified.
Treatment paradigm for metastatic clear cell renal cell carcinoma (mccRCC) has changed dramatically over the recent decades. From cytokines, interleukin-2 and interferon-α to tyrosine kinase inhibitors and mammalian target of rapamycin inhibitors, during the last decade, combinations of immune checkpoint inhibitors have taken over first-line treatment of mccRCC. These combinations are approved based on results from large phase III clinical trials, all of which used sunitinib as the comparator. These trials include CheckMate214 (ipilimumab plus nivolumab), KEYNOTE 426 (pembrolizumab plus axitinib), JAVELIN Renal 101 (avelumab plus axitinib), CheckMate 9ER (nivolumab plus cabozantinib), and the CLEAR study (lenvatinib and pembrolizumab). Results from these studies constitute milestones for newer therapeutic approaches in mccRCC. The broadening spectrum of treatment options for patients with mccRCC with multiple first-line options currently available also means that treating physicians will need to consider each option carefully, balance clinical factors, financial considerations, and weigh toxicity profiles of each drug before deciding the optimal treatment regimen for each individual patient. We describe each frontline treatment option in detail through this review to aid the decision-making process.
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