Publications by authors named "Denise Dunkley"
Background: Cervical cancer is the fourth most common cancer in women, with an estimated 342,000 deaths worldwide in 2020. Current standard of care in the UK for locally advanced cervical cancer is concurrent chemoradiotherapy with weekly cisplatin, yet 5-year overall survival rates are only 65% with a distant relapse rate of 50%. Inhibitors of Apoptosis Proteins (IAPs) are often overexpressed in cancer cells and associated with tumour progression and resistance to treatment.
View Article and Find Full Text PDFBackground: Bladder and urinary tract cancers account for approximately 21,000 new diagnoses and 5,000 deaths annually in the UK. Approximately 90% are transitional cell carcinomas where advanced disease is treated with platinum based chemotherapy and PD-1/PD-L1 directed immunotherapy. Urinary tract squamous cell carcinoma (UTSCC) accounts for about 5% of urinary tract cancers overall making this a rare disease.
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- The PI3K/AKT/PTEN pathway is often disrupted in metastatic castration-resistant prostate cancer (mCRPC), leading to an exploration of new treatments like capivasertib combined with docetaxel.
- The ProCAID phase 2 trial found that while capivasertib did not improve progression-free survival, it significantly enhanced overall survival (OS) for patients receiving the treatment, particularly for those who had previously undergone androgen receptor-targeted therapy.
- The median OS increased from 20.3 months (placebo) to 25.3 months (capivasertib), indicating that this combination could be a promising strategy for extending life in mCRPC patients.
Purpose: Preclinical data indicate that DNA methyltransferase inhibition will circumvent cisplatin resistance in various cancers.
Patient And Methods: SPIRE comprised a dose-escalation phase for incurable metastatic solid cancers, followed by a randomized dose expansion phase for neoadjuvant treatment of T2-4a N0 M0 bladder urothelial carcinoma. The primary objective was a recommended phase II dose (RP2D) for guadecitabine combined with gemcitabine and cisplatin.
Article Synopsis
- Capivasertib is a drug being tested as an addition to chemotherapy (docetaxel) for treating metastatic castration-resistant prostate cancer (mCRPC) based on encouraging preclinical results.
- In a phase II trial, patients were randomly assigned to receive either capivasertib or a placebo alongside docetaxel, with the goal of assessing whether capivasertib could prolong progression-free survival (cPFS) and overall survival (OS).
- Results showed that while median OS was significantly better with capivasertib (31.15 months) compared to placebo (20.27 months), there was no significant improvement in cPFS, suggesting further investigation is needed to confirm the findings.
Background: Urothelial bladder cancer (UBC) accounts for 10,000 new diagnoses and 5000 deaths annually in the UK (Cancer Research UK, http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/bladder-cancer , Cancer Research UK, Accessed 26 Mar 2018).
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