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Beyond the Ovary: Understanding Ovarian Cancer Metastasis

[read time: 4 min approx.]

How is it that someone can have ovarian cancer in their liver, lung cancer in their bones or testicular cancer in their stomach? The short answer: it spreads through a process of metastasis.

What is metastasis and how does metastatic cancer occur?

Metastasis is the spread of cancer from its original site to other parts of the body. Metastatic cancer is associated with stage IV or more advanced cancer stages [3]. If cancer spreads from one site, such as the ovary, to other parts of the body, it is still considered ovarian cancer.

Metastasis and ovarian cancer:

Ovarian cancer symptoms can mimic common ailments such as bloating [5] and often there aren’t apparent symptoms during the earliest stages of the disease. As there is no early detection test for ovarian cancer, many are diagnosed in the later stages when the cancer has already spread or metastasised which makes it much more difficult to treat. These factors contribute to ovarian cancer having the low survival rate of 49% for patients 5 years from diagnosis [6].

But how does ovarian cancer become metastatic?

OCRF-funded researcher Associate Professor Jason Lee explains:

“Ovarian cancer is detected at late stages often when it is in a metastatic stage, where women diagnosed are more difficult to treat because:

Ovarian cancer has a unique pattern of metastasis in which cancer cells metastasise directly to the peritoneal cavity, without entering the blood vessels, because of the lack of anatomical barrier of the primary ovarian tumour.
This peritoneal metastasis then increases the chance of ovarian cancer cells spreading to more distant organs.
Metastasizing ovarian cancer cells adapt to the new environment they encounter, and this adaptation often takes advantage of processes that do not rely on genetic changes (alterations in DNA that leads to changes in protein function), but rather epigenetic changes (study of how the environment can cause changes that impact how your genes work [9]). This is one of the reasons why my laboratory is interested in better understanding epigenetic changes that occur in ovarian cancer and metastatic progression.”

Image credit: Sineth Wijekoon

Is metastasis different from ovarian cancer recurrence?

Metastasis refers to cancer that has spread, whereas recurrence refers to cancer that has returned. Sometimes cancer cells escape a patient’s initial treatment or may have been too small to detect. These cells can cluster and grow over time, prompting recurrence [7]. Recurrence occurs for approximately 70% of people diagnosed with ovarian cancer. If ovarian cancer has spread or metastasised at the time of treatment then the risk may increase of cancerous cells being left behind or undetected, and of the patient experiencing distant recurrence (the cancer coming back in another part of the body) [8].

OCRF-funded research against ovarian cancer metastasis

Due to the challenges metastasis causes in treating ovarian cancer, Associate Professor Lee’s team at QIMR Berghofer are working on a combination treatment therapy that not only stops ovarian tumour growth and metastasis but also acts as an immunotherapy. Funded by the OCRF, the team identified that two proteins found in tumours, G9a and EZH2, allow cancerous cells to thrive by protecting them from the attacks of healthy immune cells. By using a drug combination to stop these proteins, immune cells are reactivated to fight off cancer cells and stop them spreading. In 2022, Associate Professor Lee’s team published findings of this promising treatment. The team was also the recent recipient of the government’s National Health and Medical Research Council’s grant to continue developing a combination drug therapy that inhibits these proteins.

Since 2016 the OCRF has funded over $14M of research with 27 projects focused on treatment and managing recurrence.

Through research such as Associate Professor Lee’s, the OCRF hope that patients will soon be able to fully embrace life after treatment — without the need for patients to look over their shoulders in fear of ovarian cancer’s return.

To find out more: