The 8th of May was world ovarian cancer day. Ovarian cancer is considered to be the most lethal gynaecological malignancy, being the fourth most common cause of cancer death in women in the developed world (1). Early stage misdiagnosis is common, especially since symptoms (such as feeling bloating, abdominal pain, difficulty eating or constipation) can be incorrectly attributed to common stomach and digestive complaints. Indeed, of the approximately 7000 new cases diagnosed in the UK each year, only a small percentage of diagnoses (around 20%) (2) will be early stage where the survival rate is over 90%. The key to successful early diagnosis lies in the frequency and the number of symptoms a woman suffers.
Risk factors and diagnosis:
Common risk factors include: menopause (this being the most significant risk), mutations in genes associated with DNA repair like BRCA1 and BRCA2 genes, family history, infertility or having fertility treatment, endometriosis or being overweight.
There is unfortunately no accurate screening to diagnose ovarian cancer. Current screening practices rely upon CA125 (a tumor marker that can be detected in the blood) screening, alongside abdominal and transvaginal ultrasound (3). However, CA125 screening lacks both specificity and sensitivity. Specifically, CA125 can be detected in a range of cancers and in benign conditions in premenopausal women like endometriosis, pelvic inflammatory disease or even pregnancy, it is also more accurate for late stage diagnosis.
The standard of care for patients with advanced disease involves surgical tumour debulking followed by chemotherapy but sadly most patients will relapse within 18 months and eventually will die from the disease. Over the years clinical trials have been set up to explore combinations of drugs which could improve the prognosis for ovarian cancer patients. One of these therapies is called targeted cancer therapy or biological therapy and involves stopping tumour growth through interfering with tumour biology. Tumours need to spread out to find oxygen and nutrients, a process called angiogenesis (this being crucial for tumour growth and proliferation). Several anti-angiogenic drugs have been developed and are now being tested in preclinical and clinical settings. The aim is to target not the tumour but the surrounding structures (blood vessels) necessary for tumour growth. VEGF is a molecule which is overexpressed in most solid tumours including ovarian cancer and is crucial in tumour angiogenesis. So this molecule represents a good drug target, the rationale being that inhibition of VEGF may eliminate or delay tumour growth. Bevacizumab (Avastin) is a monoclonal antibody that binds VEGF and sequesters it, causing blood vessels growth to stop, thus making it more difficult for the tumour to grow. It is the only anti-angiogenic drug licenced to be used in women with advanced ovarian cancer alongside chemotherapy. However, despite promising results in initial studies it has so far not proved beneficial to overall survival rates and some people consider it not to be cost-effective (4).
Another targeted cancer therapy used to treat ovarian cancer is inhibition of PARP1 (a molecule involved in DNA repair). This drug is called olaparib and is offered to patients with deficient tumour suppressor proteins BRCA1 and BRCA2 since cells deficient in BRCA1/2 are more sensitive to PARP1 inhibitors. PARP1 and BRCA1/2 are involved in repairing broken DNA, in patients carrying BRCA mutations, inhibition of PARP1 results in cumulative DNA damage and tumor cell death.
There are also a range of antivascular agents (drugs which attacks the blood supply of a tumor) now entering clinical trials (5). We are also making advances in immunologic therapies and in drugs targeting relevant gene mutations but, in some cases, toxic side effects make these treatments unfeasible.
Despite advances in drug research, early-stage detection is still believed to be the key to improved survival. Therefore continued research into biological markers for early detection and diagnosis is vital. It is hoped that such research, alongside work into finding biomarkers that predict disease progression, drug response and allow us to select patients who benefit the most from a specific treatment option will give us a fighting chance against ovarian cancer.
- Paik ES, Lee Y-Y, Lee E-J, Choi CH, Kim T-J, Lee J-W, et al. Survival analysis of revised 2013 FIGO staging classification of epithelial ovarian cancer and comparison with previous FIGO staging classification. Obstetrics & Gynecology Science. 2015 ;58(2):124-34.
- Hennesy BT, Coleman RL, Markman M. Ovarian cancer. Lancet 2009. 17;374:1371-82
- Jayson GC, Khon EC, Kitchener HC, Ledermann JA. Ovarian Cancer. Lancet 2014. 2014;384:1376-88.
- Robert H. Carlson. Antiangiogenic Therapy’s Value in Ovarian Cancer Questioned. Oncology Times 12/25/14
- Bell-McGuinn K, Konner J, Tew W, Springgs DR. New drugs for ovarian cancer. Ann Oncol. 2011 Dec;22 Suppl 8:viii77-viii82. doi: 10.1093/annonc/mdr531.
Links of interest:
UK CR. Ovarian Cancer incidence by UK region 2015 [cited 2016 07.01]. Available from: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/ovarian-cancer/incidence#ref-0.
Post By: Cristina Ferreras