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New role for ‘old-timer’ cancer gene

Scientists have revealed a brand new function for one of the first cancer genes ever discovered, in a finding that could open up exciting new approaches to treatment.

First identified as a cancer gene around 30 years ago, the retinoblastoma gene, also called RB1, is already known to play a central role in stopping healthy cells from dividing uncontrollably. Fault-causing RB1 mutations are found in many common cancers.

Now new research has found that RB1 has another important function, in helping to ‘glue’ severed strands of DNA back together. Faulty RB1 mutations can prevent the effective fixing of these broken DNA strands - leading to more aggressive forms of cancer.

The research, which has just been published in the journal Cell Reports, was led by Worldwide Cancer Research grant holder Professor Sibylle Mittnacht at the UCL Cancer Institute and Dr Paul Huang at The Institute of Cancer Research, London.

“We are very excited about this new discovery, [which] points to exciting prospects for new and more effective ways in which these cancers can be treated,” says Professor Mittnacht.

A long story

RB1 was first discovered in the 1980s through studies of the rare children’s eye cancer retinoblastoma. Around half of all retinoblastoma cases are caused by inherited mutations to the RB1 gene.

After years of research scientists now know that numerous common cancer types also have RB1 mutations, including hard-to-treat cancers such as triple-negative breast cancer, small cell lung cancer, glioblastoma, and aggressive types of prostate cancer. They also long-ago established that RB1 can regulate cell division, and it is this function which is traditionally linked to the cancer-causing effect of RB1 mutations.

In this new study researchers deleted the RB1 gene from lab-grown human and mouse cancer cells, and looked at how this affected DNA repair - a key mechanism cells use to protect against cancer.

They found substantially more DNA damage in cells that lacked RB1. This damage includes DNA breaks and chromosome problems, and suggests that cells with RB1 faults might find it difficult to repair damaged DNA. Importantly this new role for RB1 is completely independent of its cell division role.

“The retinoblastoma gene was one of the first cancer genes to be discovered and is one of the best known of all, so it’s very exciting to have been able to identify a completely new function for it,” says Dr Huang. “The retinoblastoma gene is famous for helping control cell division, but we found that it has another important job in gluing broken strands of DNA back together.”

The researchers think that faulty DNA-repair mechanisms caused by the RB1 mutations might lead to more aggressive and therapy-resistant forms of major cancers such as breast and lung cancers. But it's not all bad news. These findings also suggest that some existing drugs might well be effective against tumours with mutations in RB1.

“Our research could have real implications for cancer patients, because drugs that exploit weaknesses in DNA repair already exist, and there is now a rationale for testing them against cancers with retinoblastoma gene mutations,” says Dr Huang.

There's a long way to go, but we think it's an exciting step forward.

“Just like it would be impossible for a mechanic to fix a car without knowing how it worked; scientists can’t find new treatments for cancer without understanding the broken genes," says Dr Helen Rippon, Head of Research at Worldwide Cancer Research.

"Researching the nuts and bolts of cancer biology is crucial if we are to bring a brighter future for people diagnosed with the disease, and we are delighted to have helped fund this important study.”

Further information

The study was funded by a range of organisations including Worldwide Cancer Research, Cancer Research UK, the Wellcome Trust and The Institute of Cancer Research (ICR).

The original scientific article can be downloaded for free here.

You can read more about Sibylle Mittnacht’s Worldwide Cancer Research project here.

This post was adapted from a press release produced in conjunction with the ICR. Read more about this research at the ICR blog here.

2 responses to “New role for ‘old-timer’ cancer gene”

  1. […]  Recent findings from Professor Sibylle Mittnacht’s grant at University College London has shown a new role for the RB1 gene in retinoblastoma.  Her results point to exciting prospects for new and more effective ways in […]

  2. […]  Recent findings from Professor Sibylle Mittnacht’s grant at University College London has shown a new role for the RB1 gene in retinoblastoma.  Her results point to exciting prospects for new and more effective ways in […]

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