How precision medicine is transforming ovarian cancer treatment

The past twenty years has seen an unprecedented innovation in the treatment of ovarian cancer. Advancements in genomic testing and the development of new immunotherapy and targeted therapy treatments have been the driving force of this ‘precision medicine’ revolution.

We sat down with Dr Jonathan Krell, Consultant Oncologist specialising in breast and gynaecological cancers at LOC Leaders in Oncology Care, part of HCA Healthcare UK, to understand more about precision medicine, including the vital role of genomic testing, the rise of novel immunotherapies and targeted therapies, and how this combined approach has changed the way ovarian cancer is diagnosed and treated, and what these advancements mean for the future.

How is ovarian cancer is treated and how has this changed in recent years?

Traditionally, ovarian cancer has been treated with a combination of surgery and chemotherapy, and this approach continues to be highly effective in many patients. But for those patients who haven’t responded to standard therapies, or who have advanced disease, targeted therapies and immunotherapies are offering viable alternatives and additions to standard line treatments.

What’s important here is that not only do we have at our disposal a far greater number of anti-cancer therapies than ever before, but these novel therapies are not forms of chemotherapy. The significant difference being that chemotherapy uses powerful chemicals to destroy or reduce cancer cells, which damages healthy cells at the same time and results in the unpleasant side effects.

The benefit of targeted treatments and immunotherapies is that they specifically target cancer cells which, as well as being a more effective way to seek and destroy cancer cells, these therapies leave healthy cells untouched, so there is a reduction in toxicity and side effects which of course has a huge impact on our patients and their quality of life whilst receiving their cancer treatment.

How do you determine which patients should receive these novel therapies?

One of the ways we can tailor treatment is through genomic testing, which helps us to understand more about their individual cancer by looking closely at its genetic make-up. Even when people have the same type of cancer, like ovarian cancer, the cells of their cancer can have different gene changes, making one person's ovarian cancer different from somebody else’s.

Genomic testing is a type of advanced diagnostic test, referred to as molecular diagnostics. These tests look at the behaviour of the genes within individual tumour tissue and can tell us if their cancer makes specific hormones or proteins. The presence of these genes, hormones and proteins help us understand the likely behaviour of the tumour. Most importantly, these results can also provide us with valuable insights into which treatment options may be most effective for somebody’s individual tumour, such as immunotherapies and targeted therapies.

Genomic testing can also identify if a patient is eligible for a clinical trial, providing patients with direct access to cutting-edge therapies at the earliest opportunity.

At HCA Healthcare UK we have a dedicated molecular diagnostic lab, which means we have the expertise and in-house tests to provide these important genomic insights for individual cancers. 

Can you tell us more about immunotherapy and more about how this treatment works?

Immunotherapies are drugs which work with our own immune system, in particular our T-cells, boosting them so that cancer cells can be destroyed more effectively.

T-cells are integral to our immune system, their job is to recognise infection and disease and remove it from our body, like they would with the flu for example, which means that T-cells are a major threat to cancer. In response to this threat from our T-cells cancer is able to cleverly disguise itself, hiding under a shield and escaping. Our T-cells then fail to acknowledge cancer as a threat, allowing it to grow in our bodies.

Immunotherapies are very smart treatments which manipulate and strengthen our T-cells, enabling them to remove cancers shield and target cancer cells with their natural cancer destructing ability.

In some gynaecological cancers, such as endometrial cancer, immunotherapy is now used as standard of care. Studies of immunotherapy in ovarian cancer are ongoing and scientists believe there is much more to learn about how immunotherapy can be used to treat ovarian cancer. However, we do know that there are some patients, with certain tumour characteristics like PDL1 expression, that appear to benefit more than others.

There is also great promise of immunotherapy in combination with other targeted therapies for the treatment of ovarian cancer and trials of these are ongoing. Other forms of immunotherapies, like T-cell therapy, vaccine therapies and dendritic cell therapies are also being extensively studied with promising early results.

How do targeted therapies differ from immunotherapies?

Both immunotherapy and targeted therapy are types of precision medicine because they have a very focused approach. But where immunotherapy uses our body’s own immune system to target cancer, targeted therapy is a type of cancer treatment which uses drugs designed to "target" cancer cells.

In a sense targeted therapy is similar to chemotherapy because it is a drug used to treat cancer. But whereas chemotherapy effects all cells, meaning that when a patient is treated using chemotherapy it also damages healthy cells as well as cancer cells, targeted therapy is designed to target cancer cells more precisely; causing minimal affect to any surrounding healthy cells and therefore minimising the side effects of treatment.

Targeted therapies are sometimes used to treat ovarian cancer that has spread to other parts of the body, they can be given on their own or with chemotherapy.

Can you explain to us how targeted therapy works?

Every cell in our body contains genes which are part of each cell’s DNA and tell the cell what to do. Cancer cells have alterations in their genes which make them different from healthy cells; in cancer cells these genes can allow the cell to divide and grow quickly, for example. 

But not all cancer cells are the same. Ovarian cancers and, say prostate cancers for example, will have different gene changes which help those different cancers grow and spread. And those gene changes will also differ amongst people with the same cancer. Meaning one person’s ovarian cancer will not be the same as another’s, which is why personalised medicine is so important.

In addition, we now know that linked to these gene changes there are certain types of proteins or enzymes found in and around certain cancer cells, which enable them to thrive. These proteins and enzymes are responsible for sending messages which tell the cancer to grow and copy itself.

Armed with this information we have been able to create drugs which zero in on these specific proteins or enzymes and stop the messages being sent. We can block the signals which make cancer cells grow, or can provide signals which tell the cancer cells to destroy themselves.

What targeted therapies are used to treat ovarian cancer?

There are two groups of targeted therapies which have been approved for the treatment of ovarian cancer, these are PARP inhibitors and Angiogenesis Inhibitors.

Let’s look at PARP Inhibitors first, these are targeted agents which prevent ovarian cancer cells from being able to repair themselves. These drugs do this by blocking a protein called poly adenosine diphosphate-ribose polymerase, or PARP, whose job it is to fix mistakes in DNA. When targeted therapy blocks the PARP protein the ovarian cancer cells can’t fix their damaged DNA and cancer cells die as a result.

There are three PARP inhibitors that have been approved for the treatment of epithelial ovarian cancer, which is the most common type of ovarian cancer, which are olaparib, niraparib and rucaparib. Studies are also looking at the use of PARP inhibitors in conjunction with other targeted and immunotherapies. 

Moving onto angiogenesis inhibitors. When our bodies create new blood vessels this process is called angiogenesis. Solid cancer tumours need a blood supply to grow and thrive, so angiogenesis is a vital part of ovarian cancer growth. Angiogenesis inhibitors are drugs that slow down and block the development of new blood vessels which in turn starves ovarian cancer tumours and kills them.

One of the angiogenesis drugs which has been approved for the treatment of certain patients with epithelial ovarian cancer is bevacizumab. Bevacizumab is an antibody therapy that targets and destroys specific proteins produced by cancer cells, such as vascular endothelial growth factor (VEGF), which is responsible for the development of the new blood vessel formation needed by cancer to stimulate blood supply to the tumour.

There is also another class of angiogenesis inhibitor called tyrosine kinase inhibitors which are given as tablets. These have also shown great promise in the treatment of ovarian cancer, both alone and in combination with other targeted therapies.

Should all ovarian cancer patients be offered immunotherapy or targeted therapy?

Immunotherapy or targeted therapy isn’t suitable for everybody, however for some patients we're seeing increasingly positive outcomes. If you have been diagnosed with cancer your consultant will be able to tell you if they think immunotherapy or targeted therapy could form part of your treatment plan.

Now that we have access to these newer therapies, is chemotherapy still important?

Absolutely. Chemotherapy is still very much the linchpin of ovarian cancer treatment. Targeted therapies and immunotherapies aren’t suitable for everybody but they are giving us more options for certain patients, and are showing great promise in helping to prolong survival for some patients. In many cases these therapies are used in conjunction with chemotherapy, either as part of initial treatment or as part of a maintenance therapy plan.

What does all this mean for ovarian cancer patients?

These advancements are not only changing the lives of the people being treated today, but hold great promise for the future of ovarian cancer treatment.

Breakthroughs in recent years have significantly changed how we approach and treat ovarian cancer. These advancements in medicine mean that ovarian cancer patients diagnosed today have access to more treatment options than ever before and researchers are developing more targeted drugs as they learn more about specific changes in cancer cells, which is hugely promising for the future treatment of the disease.

The more we understand about the genetic makeup of individual tumours, the more we can guide patients towards more effective and kinder therapies, and our ultimate aim is to offer patients access to the personalised treatment that's right for them.

Find out more about ovarian cancer diagnosis and treatment, and other gynaecological cancers