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How Biomarkers Can Be Used In The Battle Against Ovarian Cancer

Biomarkers can be used as a tool for ovarian cancer diagnosis.

 DR. BECCY CORKILL

Dr. Beccy Corkill

 DR. BECCY CORKILL

Dr. Beccy Corkill

Custom Content Manager

Beccy is a custom content producer who holds a PhD in Biological Science, a Master’s in Parasites and Disease Vectors, and a Bachelor’s in Human Biology and Forensic Science.

Custom Content Manager

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Over 19 million new cases of cancer were reported worldwide in 2020.1 For women*, one of the most common types of cancer is ovarian cancer, with more than 310,000 people being diagnosed with the disease worldwide each year.1 Like most cancer types,2 age is a risk factor for ovarian cancer, but it can affect younger people too.3  

While survival rates for ovarian cancer have reassuringly improved in recent years,4 the survival rate of ovarian cancer is still relatively poor compared to other gynaecologic cancers.5,6,7 One of the main reasons is because ovarian cancer is hard to spot in the early stages and symptoms are nonspecific, meaning it can often go unnoticed.8 If a rapid diagnosis isn’t reached, the cancer may be more advanced and harder to manage.9,10 The ongoing COVID-19 pandemic has also put a huge strain on healthcare systems, leading to fewer patients seeing their doctors in certain parts of the world,11 further causing delays to ovarian cancer diagnoses.12

No two people are the same and no two cancers are the same. Each individual cancer is unique and possesses different biological characteristics.13 A personalised approach using different tests and diagnostics is needed to find the best way to deal with each person’s cancer.14 This is why biomarkers can be so important.15

What Are Biomarkers? 

Biomarkers are measurable indicators of some kind of biological state or activity in your body.16 Examples of biomarkers include specific cells, molecules, genes, enzymes, or hormones whose presence can indicate a disease or infection, and its severity, as well as your risk of developing a disease.17,18 In cancer care, the presence of a biomarker can be a clue that doctors can use to understand if a person is at higher risk of developing cancer, if they have cancer, and if so, its risk of progression.15,19

Since each individual cancer is unique, not all people respond to cancer management in the same way.20 To get a better understanding of a person’s cancer, doctors can carry out a biomarker test, also referred to as a “molecular test” or “genomic test” to determine the presence of biomarkers in their blood, other body fluids, or tissue.15

Doctors can use the presence of certain biomarkers to gain an understanding of people’s genetic differences and their cancers. This knowledge can help doctors tailor care plans for each specific patient.15

Biomarkers and Ovarian Cancer 

The Homologous Recombination Repair (HRR) pathway is the process through which proteins repair damaged DNA inside a cell, and changes to the pathway can lead to diseases including cancer.21 As such, genes involved in the HRR pathway have been identified as actionable biomarkers in cancer research and their presence can help doctors to tailor care plans.15

In ovarian cancer, there are several genetic biomarkers associated with a defective HRR pathway including BRCA (BReast CAncer gene), ATM (Ataxia telangiectasia mutated), BARD1 (BRCA1 Associated RING Domain 1), and BRIP1 (BRCA1 Interacting Protein 1).22 Any one of these can be a genetic variant present in tumours and as such make them indicators of disease for doctors to screen for.22

The BRCA gene may be a target for screening as certain mutations can increase a person’s risk of developing ovarian cancer.23 This is because the BRCA gene encodes proteins that help repair damaged DNA.23 If a person is positive for a BRCA mutation, this may help direct doctors towards a cancer care plan for that patient.24

Another example of a biomarker used in the management of ovarian cancer is CA125 (cancer antigen 125).25 CA125 is a protein that can be found on the surface of ovarian cancer cells, as well as some normal tissues.26 A blood test that measures the amount of CA125 in the bloodstream can be used to judge how active the tumour is and check for cancer recurrence.27

The CA125 test can be used to screen for ovarian cancer, which has the potential to improve outcomes in many lives.28 However, the test is far from fool proof as many non-cancerous conditions may also raise the level of CA125 in the blood.27 As such, a CA125 test isn't accurate enough to be used for ovarian cancer screening in general and hasn't been shown to improve the outcome for those with ovarian cancer but is often used to see how the tumour is responding post-treatment.27  

Doctors can also screen for the Human Epididymis Protein 4 (HE4) biomarker, a protein that is produced by most, but not all, epithelial ovarian cancer cells.29 HE4 can also be tested for in combination with CA125 to improve the sensitivity and specificity of ovarian cancer diagnosis.30

In 2009, the US Food and Drug Administration (FDA) approved OVA1 as another biomarker blood test that evaluates serum concentrations of five markers: CA125 II, β-microglobulin, apolipoprotein A1, prealbumin, and transferrin.31 CA125 and β-microglobulin are upregulated (they can be found at higher levels) in ovarian cancer, whereas apolipoprotein A1, prealbumin, and transferrin are downregulated (they can be found at lower levels), making OVA1 an effective screening tool. This means doctors can use this test to identify patients with a positive result and refer them for further investigation.31 

After gathering insights from the biomarker tests, doctors will decide the best course of action to take. Their findings can help them to decide upon the best route for care or weigh up management options to ease symptoms and control progression for as long as possible.15,32  

There are a number of options available, including chemotherapy, where medicine is used to kill cancer cells, and surgery to remove the cancer tissue.33 Some have chemotherapy on its own or combined with surgery.34 Other options include hormone therapy, which deprives ovarian cancer cells of the hormones they need to grow, and radiotherapy, where radiation is used to remove cancer cells or keep them from growing.35

The Future of Ovarian Cancer Biomarker Testing 

Scientists are constantly looking for new potential biomarkers for the diagnosis and management of ovarian cancer. One particularly exciting avenue of research is using artificial intelligence (AI) and biomarkers to identify those most at risk of certain cancers. By closely looking at microscopic images of tumours, AI can pick up on patterns not seen by other methods and potentially notice new biomarkers.36,37  

Fortunately, survival rates for ovarian cancer have significantly improved in recent decades.4,38,39 Although, as mentioned, outcomes for ovarian cancer remain relatively poor compared to other gynaecologic cancers.5,6,7 In the United States for instance, the mortality rate for ovarian cancer declined 33 percent between 1976 and 2015, a finding attributed to reductions in incidence and improvements in treatment.38  

A significant amount of this success can be put down to advancements in the number and variety of management options and biomarker testing.33,35,40,41 While the COVID-19 pandemic has reduced rates of biomarker testing and diagnoses,42 our increasing understanding of biomarkers is helping to improve the diagnosis and outcome of ovarian cancer for a growing number of people.40,43

*This refers to people who were assigned female at birth.

This article includes sponsored material. Read our transparency policy for more information. 

The content of this article is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of qualified health providers with questions you may have regarding medical conditions. Information in this article was correct on the date of publishing.

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12. L. S. Jacome, et al. Impact of COVID-19 Pandemic on Ovarian Cancer Management: Adjusting to the New Normal. Cancer Management and Research. 2021; 13: 359-366.

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23. J. Wu, L-Y. Lu & X. Yu. The role of BRCA1 in DNA damage response. Protein Cell. 2010; 1: 117-123.

24. National Cancer Institute. Tumor Markers in Common Use. Available at https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list Accessed March 2023.

25. P. Charkhchi, et al. CA125 and Ovarian Cancer: A Comprehensive Review. Cancers. 2020; 12: 3730.   

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30. T. Zhao, et al. CA125 and HE4: Measurement Tools for Ovarian Cancer. Gynecologic and Obstetric Investigation. 2016; 81: 430-5.

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41. J. Wu. Improved survival in ovarian cancer, with widening survival gaps of races and socioeconomic status: a period analysis, 1983-2012. J Cancer. 2018; 9(19): 3548-3556.

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Document number: Z4-39102                   

Date of preparation: March 2023                                                               


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