Scientists dismantle cancer piece-by-piece to reveal its weak spots

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Scientists are one step closer to effectively treating cancer after a team led by the Wellcome Sanger Institute broke its genetics down and found its weak spots


Scientists have dismantled cancer piece-by-piece and found its weak spots, in a possible breakthrough. 

In one of the largest studies of its kind ever conducted, researchers turned off every genetic instruction inside 30 types of cancer.

And they discovered 600 genes that can be targeted by drugs that won’t damage healthy cells in the body.

Treatments such as chemotherapy attack the whole body leading to unwanted side effects, including hair loss, nausea and fatigue.

But the findings from the study, described as ‘powerful’ by Cancer Research UK, could lead to a treatment without those gruelling effects. 

Scientists are one step closer to effectively treating cancer after a team led by the Wellcome Sanger Institute broke its genetics down and found its weak spots

Dr Fiona Behan, co-author of the study, told the BBC: ‘This is so important because currently we treat cancer by treating the entire patient’s body. 

‘We don’t target the cancer cells specifically.

‘The information we have uncovered in this study has identified key weak-spots of the cancer cells.’

She added it will allow scientists ‘to develop drugs that target the cancer and leave the healthy tissue undamaged’.

Researchers led by the Wellcome Sanger Institute disrupted nearly 20,000 genes in more than 300 cancer models in a laboratory. 

They focused on common cancers, such as lung, colon and breast, as well as ones where treatments are urgently needed such as pancreatic.

Several thousand key genes that are crucial for cancer to survive were found. The results were published in the journal Nature.

The team narrowed them down to 600 that are the most promising for developing treatment for. 

One of these is Werner syndrome RecQ helicase, also known more simply as WRN.

Cancers with a faulty DNA pathway need WRN to keep thriving, but if it can be targeted with drugs, the cancer wouldn’t survive.  

WRN is present in around 15 per cent of colon cancers and 28 per cent of stomach cancers, but there are no drugs that target it.

Another gene was Herceptin, found in breast cancer, which is already a target of some treatments, which reassured the team that their findings were correct. 

HOW COULD TARGETED DRUGS END SIDE EFFECTS OF CANCER TREATMENT?

Chemotherapy damages dividing cells – radiotherapy is usually a local treatment that only attacks the part of the body being treated. 

Cancer cells divide much more often than most normal cells. So chemotherapy damages cancer cells and can destroy them.

But some types of normal cells divide very often too. This happens in tissues that need a steady supply of new cells, such as the skin, hair and nails.

Chemotherapy can also damage those cells, and this causes side effects. But the damaged normal tissues can repair themselves and recover.

The most common side effects are to the nerves, tiredness, infections, hearing, breathing, appetite and drinking, kidneys, liver, heart and lungs, fertility, sickness, hair, skin, nails and the brain function.

For some people, chemotherapy can cause long term changes in the body.  

Late side effects can include early menopause, infertility, changes to feeling in your hands and feet (peripheral neuropathy) and heart and lung problems.

How could targeted drug therapies change this?

Cancer cells have changes in their genes (DNA) that make them different from normal cells. These changes mean that they behave differently. 

Targeted cancer drugs work by ‘targeting’ those differences that a cancer cell has which help them to survive. 

They are currently the focus of much anticancer drug development. Many have been approved by the Food and Drug Administration (FDA) to treat specific types of cancer. Others are being studied in clinical trials.

They are not suitable for all types of cancers. They are one of the main treatment for some cancers, for example melanoma and some types of leukaemia.

Targeted cancer therapies are sometimes called ‘molecularly targeted drugs,’ ‘molecularly targeted therapies,’ ‘precision medicines,’ or similar names. 

 Source: Cancer Research UK, National Cancer Institute

It brings them one step closer to their aim of completing a ‘Cancer Dependency Map’, which will be a detailed book of every vulnerability in every type of cancer.

It would mean patients would receive more precise treatment for their condition.

Dr Mathew Garnett, co-lead author of the research, said: ‘The Cancer Dependency Map is a huge effort to identify all the weaknesses that exist in different cancers so we can use this information to empower the next generation of precision cancer treatments. 

‘Ultimately we hope this impacts on the way we treat patients, so many more patients get effective therapies.’ 

Surgery, chemotherapy and radiotherapy are commonly used to treat cancer, however some patients don’t respond to treatment and healthy tissue can be damaged because chemotherapy kills all rapidly dividing cells, including normal ones.

Targeted therapies act on specific molecular targets that are associated with cancers survival and growth.  

Scientists have been exploring new targeted therapies but producing them is difficult, costing around in the region of £1billion ($1.31bn) to develop a single drug.

But having a more detailed understanding of what genes to target in the drug could speed up the process and ensure it doesn’t fail during development – which around 90 per cent of drugs do.

Dr Francesco Iorio, co-first author, said: ‘To give a new drug the best chance of succeeding in the very final phases of clinical trials, it is crucial to select the best and most promising drug target at the beginning of the drug development process. 

‘For the first time, in a data-driven way, we provide guidance at a genome-scale on which new therapeutic targets should be put forward for the development of new anti-cancer drugs.’ 

Professor Karen Vousden, Cancer Research UK’s chief scientist, said: ‘What makes this research so powerful, is the scale.’

The team used a tool called CRISPR which enabled them to screen the cancer with precision they wouldn’t have been able to five years ago.

Professor Vousden said: ‘CRISPR provides a unique tool to accelerate discovery of oncology drug targets, and this study is a salient leap in a positive direction.

‘This work provides some excellent starting points.

‘But we should remember that studying cells in the lab doesn’t always reflect the complexities of cancer in the human body and so will not necessarily reflect how someone will respond to a drug.’  

Dr Behan is hoping to revolutionise treatments for cancer patients after her mother died from the disease.

According to the BBC, the first course of chemotherapy damaged her mother’s heart, so she was not physically strong enough to beat it when it returned.

She said: ‘I want to make a difference in a patient’s life. Even a handful of new, more effective anti-cancer drugs in the clinic or an improvement in the drug development process as a result of this research would benefit an enormous number of patients.’ 

One in two people will develop cancer at some point in their lives, the cause of one in four deaths in the UK.

This year, there will be an estimated 1,762,450 new cancer cases diagnosed in the US and 606,880 cancer deaths.



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