Cover -- Title page -- Contents -- Participants -- Additional contributors -- Declarations of personal interest -- Preface -- Section 1 Biology of gynaecological cancers: our current understanding -- 1 Morphological sub-types of ovarian carcinoma: new developments and pathogenesis -- Introduction -- Major morphological sub-types of ovarian carcinoma and relative frequencies -- Grading of ovarian carcinomas -- Serous carcinoma -- Evidence for the origin of high-grade pelvic serous carcinoma from the fallopian tube -- Mucinous carcinoma -- Endometrioid adenocarcinoma -- Clear-cell carcinoma -- Transitional carcinoma -- Undifferentiated carcinoma -- Mixed carcinomas -- Problematic areas in sub-typing of ovarian carcinomas -- The concept of type I and type II ovarian carcinoma -- References -- 2 Novel treatment strategies for targeting genetic changes in endometrial cancer -- Introduction -- Inherited endometrial cancer -- Type I and type II endometrial cancer -- Type I (endometrioid) endometrial cancer -- Type II (non-endometrioid) endometrial cancer -- Genetic alterations in endometrial cancer -- PI3K/PTEN/AKT pathway -- Microsatellite instability -- KRAS -- FGFR2 -- HER2/neu (ERBB2) and EGFR -- β-catenin (Wnt signalling) -- p53 -- Novel targeted agents -- HER2 and EGFR inhibitors -- Angiogenesis inhibitors -- mTOR inhibitors -- Future approaches -- FGFR2 inhibitors -- PARP inhibitors -- Conclusion -- References -- 3 Epigenetic biomarkers in ovarian cancer -- Introduction -- DNA methylation and gene transcription -- DNA methylation as a biomarker in ovarian cancer -- Predisposition epigenetic biomarkers -- Diagnostic epigenetic biomarkers -- Prognostic epigenetic biomarkers -- Predictive epigenetic biomarkers -- Pharmacodynamic epigenetic biomarkers -- Ovarian tumour stem cells -- Conclusion -- References -- 4 Predictive biology of ovarian cancer.

Introduction -- Biomarkers are specific to EOC sub-types -- Molecular classification of HGSOC -- TP53 is a driver mutation in HGSOC -- Platinum sensitivity in HGSOC -- Genetic heterogeneity and evolution of resistance -- Summary -- References -- Section 2 The translation of biology to the clinic -- 5 Biology of BRCA1 and BRCA2 genes and implications for cancer management -- Introduction -- The BRCA1 and BRCA2 tumour suppressor genes -- Functions of BRCA1 -- BRCA1 and DNA damage response and repair -- BRCA1 and cell cycle checkpoint control -- BRCA1 and transcriptional regulation -- Functions of BRCA2 -- Likelihood of a BRCA mutation in ovarian and/or breast cancer families -- Lifetime breast and ovarian cancer risk in BRCA mutation carriers -- Histology of BRCA-related cancers -- Other cancer risks in BRCA mutation carriers -- Patterns of inheritance -- Tissue specificity of oncogenesis -- Role of BRCA1 and BRCA2 gene testing -- Genetic testing in the UK -- Options for management -- Surveillance of BRCA mutation carriers -- The UK Familial Ovarian Cancer Screening Study -- Prophylactic surgical options -- Chemoprevention agents -- Medical management for BRCA mutation carriers -- Conclusion -- References -- 6 Implications of homologous recombination defectiveness in ovarian cancer -- Introduction -- DNA damage repair pathways -- Base excision repair -- Homologous recombination -- Defects in HR in human cancer -- BRCAness -- Targeting DNA damage repair pathways and the concept of synthetic lethality -- Potential role of PARP inhibition -- Functional testing for homologous recombination defectiveness -- Conclusion -- References -- 7 The future of PARP inhibitors in the treatment of cancer -- Introduction -- PARP enzymes -- Development of PARP inhibitors -- PARP inhibitors and the BRCA story -- Pivotal phase I and II olaparib trials.

A role for single-agent PARP inhibitors in sporadic cancer -- PARP inhibitors and high-grade serous ovarian cancers -- PARP inhibitors and basal-like, triple-negative breast cancers -- PARP inhibitors as chemo-potentiators -- Resistance to PARP inhibitors and platinum chemotherapy -- Conclusion and future directions -- References -- Section 3 Imaging and therapy: state of the art -- 8 The role of robotics and the future -- Introduction -- Conventional laparoscopic surgery in gynaecological malignancy -- Advantages of robotically assisted surgery -- 3-D vision -- Articulating instruments -- Surgeon position and tremor -- A shorter learning curve, training and virtual reality training -- Disadvantages of robotic surgery -- Cost -- Tactile feel and size of ports -- Feasibility and outcomes in gynaecological oncology surgery -- Cervical cancer -- Endometrial cancer -- Obese women and endometrial cancer -- Staging procedures -- Exenterative surgery -- Survival -- The future -- Decreasing costs -- Prospective randomised trials -- Single-port laparoscopic surgery -- Fusion of imaging -- Telerobotic surgery -- Summary -- References -- 9 'Ultra-radical' surgery in advanced ovarian cancer -- Introduction -- Surgical resection of advanced ovarian cancer -- Residual disease -- Improving cytoreductive outcome -- 'Clearing' the pelvis -- Targeting upper abdominal disease -- New sources of perioperative morbidity -- In 'expert' centres, which patients should be considered for neoadjuvant chemotherapy? -- Summary -- References -- 10 Antivascular therapy in gynaecological cancers -- Ovarian cancer and angiogenesis -- Angiogenesis inhibitors -- Bevacizumab -- Single-agent activity in ovarian carcinoma -- In combination with cytotoxic agents -- Randomised trials -- Other randomised trials -- Other pathways -- Tyrosine kinase inhibitors -- EGFR tyrosine kinase inhibitor.

VEGFR tyrosine kinase inhibitors -- VEGF-Trap -- Other anti-angiogenic agents -- Metronomic cytotoxic chemotherapy -- Thalidomide -- AMG 386 -- Enzastaurin -- Integrins as targets -- Use of CA125 measurements in patients receiving VEGF inhibitors -- Other gynaecological cancers -- Vascular disrupting agents -- Small-molecule vascular disrupting agents -- Flavonoids -- Tubulin-binding agents -- OXi4503 -- Methods of predicting response and measuring activity -- References -- 11 Oncolytic viral gene therapy in ovarian cancer -- Introduction -- DNA viruses and cancer -- Adenovirus life cycle -- Clinical trials of adenovirus gene therapy in ovarian cancer -- Mechanisms to improve selectivity -- Rb pathway targeting -- Transductional targeting -- Transcriptional targeting -- Increasing cytotoxicity -- Acute inflammation and hepatotoxicity -- Clinical trial update and conclusions -- References -- 12 Endometrial cancer: what have the clinical trials taught us? -- Introduction -- Surgery at first presentation -- Laparoscopic surgery -- Systematic lymphadenectomy -- Adjuvant therapy for endometrial cancer -- Adjuvant radiotherapy -- Adjuvant chemotherapy -- Current adjuvant chemotherapy trials -- Management of recurrent endometrial cancer -- Targeted therapies in recurrent endometrial cancer -- Uncommon histological sub-types -- Conclusion -- References -- 13 Targeting therapies in cancer: opportunities in ovarian cancer -- Introduction -- Ovarian cancer: one name, many diseases -- Molecular drivers of ovarian cancer as targets for therapy -- Challenges for drug discovery and development: the story of targeting kinases -- Targeting kinases with an established biological role in ovarian cancer -- PI3Kinase pathway -- IL-6/JAK/STAT3 pathway -- NF-κB pathway -- Targeting kinases to improve response to existing chemotherapy.

Targeting kinases with novel biological functions -- Beyond kinase inhibitors: nanoparticle delivery of siRNAs -- References -- 14 Functional imaging: from tumour biology to the clinic -- Introduction -- Available techniques -- Dynamic contrast-enhanced CT or MRI -- Diffusion-weighted MRI -- Magnetic resonance spectroscopy -- Positron emission tomography -- Ovarian cancer -- DCE-MRI -- DW-MRI -- MRS -- FDG-PET/CT -- Cervical cancer -- DCE-MRI -- DW-MRI -- MRS -- FDG-PET/CT -- Endometrial cancer -- DCE-MRI -- DW-MRI -- MRS -- FDG-PET/CT -- Lymph nodes -- DCE-MRI -- DW-MRI -- FDG-PET/CT -- Iron oxide magnetic resonance lymphography -- References -- Section 4 What questions are being asked by current clinical trials? -- 15 Current clinical trials in ovarian cancer -- Primary cytoreduction: quality criteria -- Value of the neoadjuvant approach in primary advanced ovarian cancer -- Surgical cytoreduction at recurrence -- Systemic therapy -- First-line chemotherapy: dose-dense regimens -- Intraperitoneal chemotherapy and biotherapy in first-line and relapsed settings -- The incorporation of targeted therapies into first-line and and post-first-line maintenance therapy -- Ovarian cancer sub-types with rare histology -- Studies beyond first line -- Platinum-sensitive EOC relapse (PFI longer than 6 months) -- Intermediate platinum response in EOC relapse (PFI 6-12 months) -- Platinum-resistant/refractory EOC relapse (PFI shorter than 6 months) -- Conclusion -- References -- 16 Clinical trials in cervical cancer -- Introduction -- The role of surgery -- Fertility-conservation surgery -- The role of concurrent chemoradiotherapy -- Neoadjuvant and adjuvant treatment -- Neoadjuvant chemotherapy and radiotherapy -- Adjuvant chemotherapy and radiotherapy -- Improving radiotherapy treatment -- Intensity-modulated radiotherapy.

Current trials in early-stage cervical cancer.