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New Strategies in the Treatment of Ovarian Cancer: Current Clinical Perspectives and Future Potential

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TLDR
Progress in targeting the VEGF pathway and the potential for targeting other pathways and receptors that may be activated in ovarian cancer are reviewed, including the RAS/RAF/MEK and PI3K/AKT/mToR pathways, the ErbB and IGF family of receptors, mitotic check points, and also the folate receptor.
Abstract
The treatment of ovarian cancer is set to undergo rapid changes, as strategies incorporating molecular targeted therapies begin to take shape. These are based on a better appreciation of approaches targeting the tumor microenvironment as well as specific subtypes of the disease, with distinct molecular aberrations. Targeting the VEGF pathway through bevacizumab is clearly effective, with positive randomized trials at all disease stages; targeting defective homologous recombination repair pathways with PARP inhibitors is also proving successful in a substantial proportion of patients with high-grade serous ovarian cancer. In this article, we will review progress in these two leading areas and also discuss the potential for targeting other pathways and receptors that may be activated in ovarian cancer, including the RAS/RAF/MEK and PI3K/AKT/mToR pathways, the ErbB and IGF family of receptors, mitotic check points, and also the folate receptor. Here, single-agent therapy may play a role in selected cases but essential components of future strategies should include combination treatments aimed at dealing with the key problem of drug resistance, together with rational approaches to patient selection.

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Journal ArticleDOI

Epithelial ovarian cancer: Evolution of management in the era of precision medicine

TL;DR: To improve survival in this aggressive disease, access to appropriate evidence‐based care is requisite and individualized precision medicine will require prioritizing clinical trials of innovative treatments and refining predictive biomarkers that will enable selection of patients who would benefit from chemotherapy, targeted agents, or immunotherapy.
Journal ArticleDOI

Inhibition of the PI3K/AKT/mTOR Pathway in Solid Tumors

TL;DR: To maximize therapeutic benefit, drug combinations and schedules must be explored to identify those with the highest efficacy and lowest toxicity overlap, and defining appropriate patient subpopulations, for both monotherapy and drug combinations, will be important.
Journal ArticleDOI

The folate receptor as a rational therapeutic target for personalized cancer treatment

TL;DR: Targeted therapies combined with a reliable companion diagnostic test represent a novel approach toward efficient personalized medicine for malignant and nonmalignant disorders and forms a realistic basis for the rational design and implementation of novel FR-targeted drugs for the treatment of cancer and inflammatory disorders.
Journal ArticleDOI

Targeted therapies in breast cancer: New challenges to fight against resistance.

TL;DR: The main scope of this review is to provide a thorough update of recent developments in the field and discuss future prospects for preventing resistance mechanisms in the quest to increase overall survival of patients suffering from the disease.
Journal ArticleDOI

BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer

TL;DR: The role of somatic BRCA mutations and BRCa methylation in ovarian cancer is discussed and the challenges that need to be addressed are explored if the full potential of these markers of HRD is to be utilised in clinical practice.
References
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Journal ArticleDOI

Integrated genomic analyses of ovarian carcinoma

Debra A. Bell, +285 more
- 30 Jun 2011 - 
TL;DR: It is reported that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1,BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes.
Journal ArticleDOI

Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.

Integrated genomic analyses of ovarian carcinoma

Daphne W. Bell, +261 more
TL;DR: The Cancer Genome Atlas project has analyzed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours as mentioned in this paper.
Journal ArticleDOI

Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

TL;DR: It is proposed that, in the absence of PARP1, spontaneous single-strand breaks collapse replication forks and trigger homologous recombination for repair and exploited in order to kill BRCA2-deficient tumours by PARP inhibition alone.
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Integrated genomic analyses of ovarian carcinoma

Debra A. Bell, +285 more
- 30 Jun 2011 -