Gynaecological cancers: malignancies of the cervix, uterus, ovaries, vagina and vulva, are responsible for over 1.1 million new cancer cases and almost half a million deaths annually. Ovarian cancer in particular is difficult to treat due to often being diagnosed at a late stage, and the incidence of uterine and vulvar malignancies are both on the rise. The field of nanomedicine is beginning to introduce drugs into the clinic for oncological applications exemplified by the liposomal drugs, Doxil and Myocet, the nanoparticle, Abraxane and antibody–drug conjugates (ADCs), Kadcyla and Adcetris. With many more agents currently undergoing clinical trials, the field of nanomedicine promises to have a significant impact on cancer therapy. This review considers the state of the art for nanomedicines currently on the market and those being clinically evaluated for the treatment of gynaecological cancers. In particular, it focuses on ADCs and presents a methodology for their rational design and evaluation.

Endometrial cancer (EC) is the sixth most prevalent female cancer globally and although high rates of success are achieved when diagnosed at an early stage, the 5-year survival rate for cancers diagnosed at Stages II–IV is below 50%. Improving patient outcomes will necessitate the introduction of novel therapies to the clinic. Pan-cyclin-dependent kinase inhibitors (CDKis) have been explored as therapies for a range of cancers due to their ability to simultaneously target multiple key cellular processes, such as cell cycle progression, transcription, and DNA repair. Few studies, however, have reported on their potential for the treatment of EC. Herein, we examined the effects of the pan-CDKi dinaciclib in primary cells isolated directly from tumors and EC cell lines. Dinaciclib was shown to elicit a bimodal action in EC cell lines, disrupting both cell cycle progression and phosphorylation of the RNA polymerase carboxy terminal domain, with a concomitant reduction in Bcl-2 expression. Furthermore, the therapeutic potential of combining dinaciclib and cisplatin was explored, with the drugs demonstrating synergy at specific doses in Type I and Type II EC cell lines. Together, these results highlight the potential of dinaciclib for use as an effective EC therapy.

5555 Background: Olfactory neuroblastoma is rare with 25 new cases annually in the UK. Cranio-facial resection and post operative radiotherapy is standard treatment. The use of concomitant chemotherapy has not been fully evaluated, although chemo-sensitivity has been demonstrated by retrospective series. This study evaluates the use of radical radiotherapy and concomitant chemotherapy. Methods: Since 1978 more than 70 patients have been seen at the Institute of Otology and Laryngology. Eighteen patients treated with radiotherapy between 1999 and 2005 were reviewed. These were all CT planned and treated with conformal radiotherapy ± cisplatin chemotherapy 100 mg/m² D 1, 22 and 43. The radiotherapy prescribed dose varied from 50Gy to 62 Gy in 1.8 to 2 Gy fractions, 10 (56%) received 60Gy in 30 fractions. Overall survival, disease free survival and treatment related morbidity were assessed. Results: Seventeen patients were post operative and 1 was neo-adjuvant. Mean age was 46 years (range 20–83) and the majority were Kadish stage C. Of the 17 post-operative patients, 13 (76%) had surgery as primary treatment and 4 (24%) for recurrence. Eight patients (44%) received concomitant chemotherapy. At the time of analysis follow up ranged from 4 months to 72 months (median 17.5, mean 28.2), 16 (88.9%) patients were alive and 14 (77.8%) disease free. Four (22.2%) patients developed recurrence and 2 died of disease. Of the 4 patients with recurrence, 3 did not receive concurrent cisplatin chemotherapy and the fourth patient did not undergo radical surgery. No patients reported deterioration in vision or significant morbidity following treatment. Conclusions: Post operative radiotherapy with concurrent cisplatin chemotherapy is effective and well tolerated in the management of olfactory neuroblastoma. Where concurrent chemotherapy was not given, relapse rates were high. Our results, although immature, suggest disease free survival superior to published data. A prospective multi-centre study to evaluate concomitant treatment schedules is required. No significant financial relationships to disclose.

GSK-J4 modulates EMT marker expression in OVCAR-3 but not CAOV3 cells

SiRNA-mediated knockdown in CAOV3 cells

ARV-110 and enzalutamide modulate H3K27 methylation in CAOV3 and SKOV3 cells