LARP1 post-transcriptionally regulates mTOR and contributes to cancer progression.

RNA-binding proteins (RBPs) bind to and post-transcriptionally regulate the stability of mRNAs. La-related protein 1 (LARP1) is a conserved RBP that interacts with poly-A-binding protein and is known to regulate 5'-terminal oligopyrimidine tract (TOP) mRNA translation. Here, we show that LARP1 is complexed to 3000 mRNAs enriched for cancer pathways. A prominent member of the LARP1 interactome is mTOR whose mRNA transcript is stabilized by LARP1. At a functional level, we show that LARP1 promotes cell migration, invasion, anchorage-independent growth and in vivo tumorigenesis. Furthermore, we show that LARP1 expression is elevated in epithelial cancers such as cervical and non-small cell lung cancers, where its expression correlates with disease progression and adverse prognosis, respectively. We therefore conclude that, through the post-transcriptional regulation of genes such as mTOR within cancer pathways, LARP1 contributes to cancer progression.

Sexual activity and functioning in ovarian cancer survivors: an internet-based evaluation.

OBJECTIVES: Sexual dysfunction is a known complication of treatment for many cancers, but there have been relatively few studies investigating outcomes for ovarian cancer survivors. We have previously reported that women treated for ovarian cancer experience persistent psychological and physical problems. Sexual functioning was highlighted as a significant factor and we sought to investigate this further. METHODS: Women were invited to complete a questionnaire using both paper and online response formats. A validated tool, the Sexual Activity Questionnaire, was used to obtain information from women following a diagnosis of ovarian cancer. RESULTS: Across all responders (n = 102, mean age 51.3 years), 63% of women reported their ovarian cancer diagnosis had negatively changed their sex life. The most common reasons given for an absence of sexual activity were a lack of interest in sex, physical problems that prevented sex or no partner. Of the 46% of responders who stated they were sexually active, 77% reported pain or discomfort during intercourse and 87% described vaginal dryness. CONCLUSION: For the majority of women, treatment for ovarian cancer negatively impacts on their sex lives. Many of the symptoms described by participants are potentially reversible and clinicians should be open to raising the issue of sexual functioning with their patients.

Sunitinib in the management of gastrointestinal stromal tumours (GISTs).

AIMS: Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the gut with a 5-year survival of approximately 50%. Surgery remains the treatment of choice in resectable disease, with conventional chemotherapy largely ineffective. Over 90% of GIST possesses mutations in the c-KIT oncogene, producing an overactive tyrosine kinase, which may be driving the malignant process. Imatinib inhibits the aberrant tyrosine kinase and imatinib therapy in metastatic disease has shown significant clinical benefit. However, resistance typically develops within 2 years, with the need for further therapy. This article aims to introduce the reader to a new development in cancer therapeutics. METHODS: A literature search was performed using the MEDLINE database to identify publications relevant to the review. References within these articles were used to expand the search. Abstracts from recent ASCO symposia were hand searched for relevant articles. FINDINGS: Sunitinib (SU11248) is a novel multi-targeted tyrosine kinase inhibitor with activity not only against the receptor tyrosine kinase product of c-KIT but also other cell-signalling pathways that may be relevant in GIST; FLT3, platelet-derived growth receptor (PDGFR) and vascular endothelial growth factor receptor (VEGFR). Two Phase II trials and one Phase III trial have investigated the activity of sunitinib against imatinib-resistant GIST. Early results showed significant benefits in time to disease progression that led to licensing of the drug in America and more recently in Europe. A Phase III trial comparing dose-increased imatinib and sunitinib in progressed GIST is currently planned. CONCLUSIONS: Initial clinical results with sunitinib are promising and suggest a future role. Further studies are needed before sunitinib can be recommended for the routine treatment of imatinib-refractory GIST.