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The past ten years have seen many advancements in the way we treat bowel cancer, transforming outcomes for patients. Advancements in genomic testing, immunotherapy, targeted therapies and access to clinical trials have been the driving force of this innovation.

Prof Hendrik-Tobias Arkenau, Consultant Medical Oncologist at the Sarah Cannon Research Institute and the LOC, explains more about genomic testing and how this can be used to guide personalised treatment plans.

As clinicians we are really excited about the increasing range of therapies available to treat bowel cancer and the ability to give specific, personalised treatments to patients based on the molecular characteristics of their cancer. 

This means patients will receive the treatment which is most likely to have clinical benefit based on the genetic makeup of their individual tumour.

Genomics

To understand which treatment will work best for an individual patient we firstly need to know more about the specific genetics of their cancer. We do this through genomic testing. 


What is genomic testing?

Genomic testing helps us understand more about the person’s cancer by looking closely at its genetic make-up. It can tell us if the cancer makes specific hormones or proteins that may encourage it to grow and help us understand the likely behaviour of the tumour, including how fast it will grow and how likely it is to metastasize (spread to other parts of the body). Even when people have the same type of cancer, like bowel cancer, the cells of their cancer can have different gene changes, making one person's specific type of bowel cancer different from somebody else’s.


How does genomic testing influence cancer treatment?

Some targeted therapy or immunotherapy drugs can target an individual’s specific gene changes or proteins in their cancer cells, blocking these proteins or gene changes to stop the cancer from growing and spreading. 

By using an individual patients' genomic information we can optimise their treatment plan, giving them the best available treatment for their cancer.

Importantly, 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. 

Taking part in a clinical trial can give you access to therapies now, that may become standard of care in 5 to 10 years. Many patients with advanced disease, who participated in certain immunotherapy trials, 10 years ago are still alive, whereas they might not have been if they only had access to standard care. 
 
Dr Kai-Keen Shiu, Consultant Medical Oncologist, at the LOC shares his insights into the ever-evolving field of immunotherapy, targeted therapies and personalised medicine.

The traditional combination of surgery and chemotherapy continues to be highly effective in treating bowel cancer 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.

Immunotherapy

What is immunotherapy?

Immunotherapies are treatments which use our own immune system, specifically our T-cells, to recognise and attack cancer, T-cells are integral to our immune system. They are programmed to recognise infection and disease and eradicate it from our body, like they would with the flu for example. T-cells are a major threat to cancer, so it cleverly disguises 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.


How does immunotherapy work?

Immunotherapy works by manipulating our own immune system to see through the shield and recognise and target cancer cells. Immunotherapies are infused through a drip into the patients’ bloodstream (as we would with chemotherapy), they then harness and strengthen our T-cells natural cancer fighting abilities.

What’s the latest breakthrough in immunotherapy treatment for bowel cancer?

The latest advancement in immunotherapy for bowel cancer is a breakthrough drug which is used to treat metastatic bowel cancer in patients with a specific DNA mutation which is known as microsatellite instability high (MSI-H). This mutation can be hereditary, known as Lynch syndrome, or can occur randomly.

Whilst only around five per cent of advanced bowel cancer patients have this genetic mutation, they usually have a worse prognosis, and typically don’t respond as well to standard chemotherapy and other targeted therapies. 

This immunotherapy drug is a breakthrough because it is significantly better than chemotherapy at shrinking metastatic bowel cancers with this specific DNA mutation, and delaying the time it takes for the cancer to grow. 

Should all bowel cancer patients be offered immunotherapy?

Immunotherapy isn’t suitable for everybody, however for some patients we're seeing increasingly positive outcomes. Your consultant will be able to tell you if they think immunotherapy could form part of your treatment plan.

Targeted therapy


What is targeted therapy?

Targeted therapy is a type of cancer treatment which uses drugs designed to "target" cancer cells without affecting normal cells. Because of this very focused approach it is sometimes called precision medicine.

Targeted therapies are sometimes used to treat bowel cancer that has spread to other parts of the body. They may be given on their own or with chemotherapy. Your consultant will be able to tell you if they think a targeted therapy could form part of your treatment plan.

Is it different to chemotherapy?

Chemotherapy effects all cells, meaning that when a patient is treated using chemotherapy it also damages normal, healthy cells as well as cancer cells, which is what causes the unpleasant side effects. Targeted therapy, like chemotherapy, is a drug used to treat cancer, but it’s different to chemotherapy because it's designed to target cancer cells more precisely, causing minimal affect to any surrounding healthy cells and therefore minimising side effects.

How does targeted therapy work?

Every cell contains genes. Genes are part of each cell’s DNA which tells 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.

However not all cancer cells are the same. Bowel cancer and 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 bowel 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 bowel cancer?

There are several types of targeted therapy approved for the treatment of bowel cancer, but not all bowel cancers will respond to these drugs. Your Consultant will be able to advise on what’s best for you. 


Should all bowel cancer patients be offered targeted therapy?

Targeted therapy is an important type of cancer treatment, and researchers are developing more targeted drugs as they learn more about specific changes in cancer cells. But so far, only a few types of cancers are routinely treated using only these drugs. For most patients this means they will receive targeted therapy alongside other forms of treatment such as, surgery, chemotherapy, radiotherapy, or hormone therapy.

These advancements in medicine mean that bowel cancer patients have access to more treatment options than ever before. 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. 
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