The personal touch: genomics and the fight against cancer – Raconteur

What you now see is that every cancer is a rarecancer.

So says Emile Voest, professor of medical oncology at the Netherlands Cancer Institute, who was writing in the journal Nature. Voest was highlighting a revolutionary change in cancer treatment over the past decade: the advancement ofgenomics.

Genomics is the study of how genes interact with one another and the environment. It has already had a massive impact in oncology. For example, Voest notes that 12 years ago, lung cancer was classified as either small cell or non-small cell. Today, its identified by nearly 30 genomic mutations orchanges.

Identifying specific mutations in patients marks a radical shift from one-size-fits-all treatment towards more personalised therapy. For example, it could provide treatments for colorectal cancer with mutations in the so-called KRAS gene, which dont respond to some standard therapies. Likewise, acute myeloid leukaemia carries mutations that make it resistant to drugs known as isocitrate dehydrogenase inhibitors; genomics could offeranswers.

Cancer is far more complex than even the most visionary of scientists everimagined.

Twenty years ago, for example, researchers speculated that germ cell testicular cancer might be attributable to a single gene. However, a team led by Professor Clare Turnbull of the Institute of Cancer Research in London has found more than 40 genomic variants associated with thedisease.

Small wonder, then, that so many experts see such importance in genomics. And there has been significant progress. For example, Turnbull was clinical lead on the 100,000 Genome Project, which sequenced 100,000 genomes from more than 80,000 NHS patients with cancer or a rare disease. This yielded potential research leads in nearly half the cancer patients takingpart.

To understand why all this is so remarkable, its important to understand the context. The initial sequencing of the full human genome took more than 10 years and cost in excess of 2 billion. Using a blood sample, an individuals genome can now be sequenced in a day for less than 700.

Genomic medicine is already saving lives in a multitude of ways. Take DYPD, a gene mutation carried by roughly 10% of the UK population that can make chemotherapy harmful to the bone marrow, potentially killing the patient. Genomics advances mean doctors can now test patients for the mutation at a cost of 50 each, saving lives and cutting costs for the NHS, notes Andrew Beggs, professor of cancer genetics and surgery in the Institute of Cancer and Genomics Sciences at the University of Birmingham.

However, Beggs worries about a lack of public and even professional awareness about the scope for cancer prevention. For example, Lynch syndrome is a genetic condition that can increase the risk of bowel cancer by up to 80%. It also increases the risk of ovarian, womb and other cancers. Beggs, who runs a Lynch syndrome clinic, says its a relatively common condition, affecting about 1% of the UK population, but most are not aware ofit.

One reason for this is cultural. Most people think of the NHS as an institution they turn to when they are feeling sick, but genomic medicine points to a future when there will be an ever bigger emphasis on preventive medicine. Increasingly, families with a history of genetically linked cancers will be asked to undergo testing and any necessary treatment to prevent the cancers developing at all. But Beggs says that some patients fear screening because they do not want to face up to the idea that they could be at risk from a fataldisease.

Most people want to find out if they are at risk, but the people who dont want to know tend to be in their late teens and early 20s. You can understand this. They are young and believe it will never happen to them. But some are scared, heexplains.

The answer, he says, lies in education of both healthcare professionals and patients. GPs have a critical role to play in identifying families atrisk.

There are advantages to the NHS too. A single round of chemotherapy in a private hospital can cost up to 3,000, while cancer drugs cost the NHS more than 2bn a year. While a single genomic treatment could cost up to 20,000, thats cheaper than putting a patient through hospital admissions with say five or six rounds of chemotherapy that dont work and that cause significant side effects, Beggsnotes.

Oncology used to be like sharp-pointed sticks and rocks. We now have more finesse and have moved to the medical equivalent of ascalpel

Statins, the widely prescribed cholesterol-lowering drugs, are another example of a cheap therapy that has been found to have a beneficial effect in genomic treatment. Costing as little as four pence per tablet, statins have been shown to reduce levels of P53, a tumour suppressor gene. P53 mutations can cause cancer cells to grow andspread.

Statins are an example of repurposed drugs old medicines used in new ways that have long-established safety records. They can avoid the need for expensive new medicines. About 25,000 new substances are tested for every marketed medicine that makes enough money to pay for its development.

Genomic drug testing is also changing clinical trial design. Traditional trials usually compare one drug with another, with patients divided into treatment groups. They remain on the trial from the start to the end perhaps for several years irrespective of whether it is helpingthem.

The ongoing National Lung Matrix Trial could change this. Through the trial which is based on 11 treatment arms using different drugs University of Birmingham researchers match various treatments to different groups of lung cancer patients according to genetic changes in their cancers. If a particular drug isnt working, that treatment arm is closed and a new one may be introduced. If a patient doesnt respond to drug A, they can be switched to drug B. They may be in and out of the trial within twomonths.

In a traditional trial, patients receive broad spectrum chemotherapies that dont work half the time, Beggs says. Oncology used to be like sharp-pointed sticks and rocks. We now have more finesse and have moved to the medical equivalent of ascalpel.

Thirteen regional genomic centres are now operating in England. One of their goals is to identify the patients who may benefit most from from genomic testing. Another is to ensure more effective use of medicines, not just in cancer, but in all health care. The NHS medicines bill was about 17 billion a year. However, 50 per cent of medicines are not taken as prescribed and one in 15 hospital admissions occur because of adverse drug reactions according to a recent report in the Pharmaceutical Journal.

What is also disturbing is that the effectiveness of drugs overall ranges between 30 to 50 per cent. Advances in cancer genomics is explaining why so much conventional chemotherapy fails it does not target the right mutations. Hopefully, genomics will also lead to kinder treatments. Severe side effects arising from cancer therapy are all toocommon.

There is, of course, still a long way to go before the genomic revolution meets its full potential, but the success so far would have been unimaginable just a few yearsago.

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The personal touch: genomics and the fight against cancer - Raconteur