A new Tumour Profiling Unit at the Institute of Cancer Research (ICR) in London will spearhead research into ‘personalised’ medicine and drug resistance in cancers.

The new research centre, the largest of its kind in the NHS, will analyse tumour cell DNA to pinpoint the critical mutations that cause cancer.

The aim is to develop many ‘personalised’ drugs, such as Herceptin, that can attack cancers with a specific genetic characteristic.

Tumour samples from patients at the Royal Marsden Hospital will be repeatedly tested to identify the genetic mechanisms underlying tumour development and drug resistance.

The Tumour Profiling Unit will also store the genetic codes of cancer patients, and make the findings available to doctors and pharmaceutical companies.

Professor Alan Ashworth, the ICR’s Director, said: “None of this is science fiction. This is now happening. We think we’re pioneering the clinical application of this by setting up the Tumour Profiling Unit, but one would think this would be absolutely routine practice for every cancer patient – and that’s what we’re aiming to bring about.”

Professor Ashworth compared cancer treatment to the game ‘Whack-a-Mole’: every time a cancer drug is successful, tumours develop resistance to it. The new research unit aims to find treatments that can stop the cancer evolving.

According to a recent DH announcement, the entire genetic code of up to 100,000 NHS patients with cancer and rare diseases will shortly be sequenced to facilitate research.

Roche has abandoned its attempt to take over US biotech company Illumina after a year of increasingly bitter argument.

The pharmaceuticals and diagnostics giant has seen an increased cash offer and an attempt to take over the gene sequencing company’s board of directors fail.

Roche’s Chairman, Franz Humer (pictured), has indicated that Roche is interested in discussions with other biotech companies that have similar platforms.

Roche’s pursuit of Illumina has been likened by industry observers to Gollum’s doomed quest for his “precious” ring.

It began at the start of 2012, with Roche offering $5.7bn to acquire the US company – an offer described by Illumina as “grossly inadequate”.

Roche extended its deadline by two months and then increased the offer to $6.8bn, citing a positive “market reaction”.

The pharma giant urged Illumina’s shareholders to support the deal by electing Roche representatives to the biotech company’s board of directors.

“As a standalone company, Illumina’s future is far from certain,” commented Roche’s CEO, Severin Schwan, at that time.

However, the Illumina board’s annual meeting did not elect a majority of Roche supporters, and Illumina CEO Jay Flatley called the bid “opportunistic”.

Despite the predictions of industry experts that a deal would be struck, Humer has announced that Roche is no longer pursuing the biotech firm.

The Illumina takeover was a “nice to have”, not a “must have”, he claimed, and Roche was considering other specialists – such as Life Technologies and Oxford Nanopore Technologies – to provide its diagnostics division with a less costly gene sequencing platform.

Meanwhile, Illumina reports 20% revenue growth in the last quarter. It plans to expand into the increasingly profitable field of cancer diagnostics and targeted drugs.

Researchers in the UK and the US have developed a method of designing drugs that can act on multiple gene targets, enabling them to treat complex diseases.

The new drug development process could revolutionise the treatment of major diseases including diabetes, cancer and bipolar disorder.

Whereas current genetic therapies target individual genes, leading to a highly specialised or ‘personalised’ drug regime for the patient, the new drugs could be effective across a wide patient spectrum.

Susceptibility to complex diseases such as cancer is known to depend on a considerable number of genetic and non-genetic factors – so the impact of a drug that can treat all known genetic factors could be massive.

Ironically, this research breakthrough could reverse the trend of pharmaceutical innovation towards ‘personalised’ medicine over the last decade, renewing the role of broad-spectrum drugs in treating major diseases.

The research collaboration by scientists at the Universities of Dundee (UK) and North Carolina (US) has developed a method of computerised drug design, based on large databases of drug-target interactions.

The scientists tested 800 predicted drug-target interactions using new drugs designed by this method: 75% were confirmed by in vitro tests.

In addition, the concept of using one new drug to treat a complex disease across a range of genetic factors has been proven in mouse models.

A drug designed to treat ADHD was shown to be effective in preventing typical hyperactive behaviours in two mouse groups with different genetic defects: a missing dopamine receptor and a missing brain neuropeptide.

Study co-leader Brian L. Roth, Professor of Pharmacology at the UNC School of Medicine, commented that for a complex disease, “we know there are likely hundreds of different genes that can influence the risk for disease and, because of that, there’s likely no single gene and no one drug target that will be useful for treating it.

“And so the realisation has been that perhaps one way forward is to make drugs that hit collections of drug targets simultaneously. Here we show how to efficiently and effectively make designer drugs that can do that.”

The NHS will build a database of 100,000 human genomes to assist the development of new therapies for cancer and rare genetic diseases.

Prime Minister David Cameron announced the UK Genome Project, which will strengthen the capacity of the NHS to provide targeted drugs, as part of the Strategy for Life Sciences.

The UK will be the first country to use DNA sequences within its mainstream health service.

The genomes of over 100,000 patients with cancer or rare genetic diseases will be mapped within five years, with the potential to reduce the number of premature deaths from these conditions.

“By unlocking the power of DNA data, the NHS will lead the global race for better tests, better drugs and above all better care,” Cameron said.

The NHS will dedicate £100m over 2013–18 to fund DNA sequencing, build the database and provide training for doctors to use the information.

Harpal Kumar, Chief Executive of Cancer Research UK, pointed to Gleevec – Novartis’ drug for chronic myeloid leukaemia – as a successful example of a targeted cancer drug.

The human genome database would enable doctors and scientists to develop new ways to prevent, diagnose and treat cancers, he said.

The project was welcomed by life science industry representatives. Stephen Whitehead, Chief Executive of the ABPI, said: “The cancer genome initiative will harness the latest science and technology to take the next transformative step towards personalised medicine.

“With our strong science base, our biopharmaceutical industry and the potential of the NHS as an engine for research, the UK is in a prime position to lead on the development and delivery of personalised medicines.”

The BMA has warned against the proposed rollout of personal health budgets (PHBs) before doctors have received more information and evidence to support it.

The Department of Health plans to start allowing patients with long-term conditions to purchase NHS care packages from personal allowances.

According to a BMA survey, only 10% of doctors believe PHBs will improve clinical outcomes, while only 40% believe it will be cost-effective.

The rollout of PHBs follows a number of pilot programmes in 2009.

The BMA’s survey took responses from over 200 doctors. While 60% agreed that patients with long-term conditions should have more control over their care, 70% said they were not well informed about PHBs.

Only 20% supported the idea of PHBs, 10% thought it would improve patient outcomes, and 40% thought it would improve control of costs.

Dr Mark Porter (pictured), Chair of the BMA Council, said: “Doctors are yet to be convinced of the benefit of personal health budgets and have a number of doubts about their clinical and financial implications.

“Nevertheless, there is recognition that personal health budgets could have benefits for patients with long-term conditions. In principle, empowering individuals to play an active role in decisions around their care, in partnership with their doctors, offers a real opportunity to make the NHS more responsive to individual needs.”

He argued for a delay in the rollout of PHBs pending:

• an information campaign on PHBs for healthcare professionals

• more evidence to show the benefits of PHBs for patient outcomes

• procedures to ensure that PHBs are cost-effective.

“The BMA will seek to work with the government to make sure that patients get the best deal from any proposed introduction of personal health budgets,” Porter concluded.

The NHS is a key “national asset” for life science innovation, Prime Minister David Cameron has said.

Speaking at the inaugural Global Health Policy Summit in London, Cameron emphasised the relationship between NHS reform and the Government’s innovation strategy.

Developments such as value-based pricing and making anonymised NHS patient data available to researchers would “bring breakthroughs in long-neglected areas like dementia”, he claimed.

Cameron stated that his goal in healthcare was to make the NHS “diverse, flexible and tailored to individual needs”, thereby adapting it as a research base to the challenge of developing personalised medicine.

Global healthcare was undergoing a “fundamental shift” towards “individually-tailored” medicine, he said, driven by the growing prevalence of non-communicable diseases and the progress of genetic research.

To achieve that required “open innovation, more collaboration with universities and start-ups, and a greater emphasis on data analytics and genomics”.

The unique patient data resources and purchasing power of the NHS made it a natural partner for life science innovation, he argued.

To develop that relationship, the Government had given the NHS a legal duty to promote research, was planning to introduce value-based pricing, and was consulting on an early access scheme for new medicines.

Crucially, it planned to change the NHS constitution so that patient data could be used for research unless the patient opted out.

Stephen Whitehead, Chief Executive of the ABPI, commented that the trade association valued the Government’s “continued support for industry” and agreed that the NHS offered the life science industry a “great opportunity”.

However, he said, “we are not convinced that value-based pricing will encourage innovation or reward the most effective medicines,” as it would not reflect the incremental nature of innovation or reward the industry enough for its R&D.

The European Medicines Agency has recommended approval of the first drug to treat the underlying genetic cause of cystic fibrosis (CF).

Kaydeco (ivacaftor) from Vertex Pharmaceuticals has been recommended by the agency for people with CF aged over 6 who carry the G551D gene mutation.

The drug has the potential to help an estimated 1,100 people in Europe in whom this mutation causes CF.

In people with the G551D mutation, Kalydeco helps the defective protein synthesised by the mutant gene to function more normally.

In two major placebo-controlled phase III studies, patients taking Kalydeco showed sustained improvements in lung function, gained weight and were 55% less likely to suffer exacerbations.

Stuart Elborn, President of the European Cystic Fibrosis Society, said: “While there has been great progress in cystic fibrosis treatment during the last few decades, we are still only treating the symptoms and complications of the disease. Kalydeco is a fundamentally different approach to the way we treat cystic fibrosis because it targets the underlying cause of the disease.”

“Since 1998, Vertex has been committed to developing new medicines to treat the underlying cause of cystic fibrosis,” commented Peter Mueller, Chief Scientific Officer and Executive VP of Global R&D at Vertex. “We look forward to working with the EMA to bring Kalydeco, our first new medicine in Europe, to people with CF as quickly as possible.”

CF is a life-threatening genetic disease affecting 35,000 people in Europe.

Roche’s Zelboraf (vemurafenib) can extend the lives of patients with advanced melanoma by more than a year, data from a phase III trial has shown.

Patients given Zelboraf showed a median overall survival of 13.2 months, compared to 9.6 months with chemotherapy.

An abstract of the trial report stated that the increased survival meant a 38% reduction in the risk of death from melanoma.

A previous controlled trial, which formed the basis for the drug’s FDA approval in 2011, was halted early so that patients in the chemotherapy arm could be given Zelboraf for their clinical benefit.

Zelboraf has been hailed as a leading example of ‘personalised’ medicine as it targets the BRAF gene mutation, carried by about half of all melanoma patients.

Jennifer Low, Group Medical Director in Product Development for Genentech, Roche’s US subsidiary, commented: “The life expectancy for these patients isn’t very long, so they have an opportunity to have therapy that on average improves survival by a really significant amount.”

Roche is also testing Zelboraf as a treatment for other types of cancer, alone or in combination with other drugs.

Breast cancer tumours have been reclassified into 10 distinct types linked to genetic features, following the largest ever study of breast cancer tissue.

The study findings have implications for patient selection in clinical trials and the development of drugs targeted at specific patient populations.

Tests to identify which group a woman belongs to, enabling more specific treatment recommendations and survival predictions, are expected to be available in the NHS in three to five years.

Researchers in the UK and Canada analysed DNA and RNA samples from breast cancer tumours in 2000 women. Through genetic profiling, they found 10 subtypes of tumour with genetic features that correlate with survival.

Carlos Caldas of Cancer Research UK’s Cambridge Research Institute said the study meant that breast cancer was an “umbrella term”.

“It is not going to change the management of women treated in the NHS tomorrow, but it is surely going to change the way in which we do clinical trials,” he commented. “We will be doing clinical trials that are much more targeted at each of these 10 subtypes.

“And finally, because we have discovered new breast cancer genes, this will give us new avenues to develop targeted treatments.”

The study identified genes for enzymes active in tumour growth – which make good targets for drug therapy because their receptor sites can be targeted.

Breast cancer is currently classified into four types according to whether the tumour is positive for receptors for oestrogen (Er+), human epidermal growth factor receptor 2 (Her2+), or progesterone (Pr+).

Targeted drugs exist for Er+ and Her2+ tumours. Tumours that are negative for all three receptors have a very poor prognosis.

The study allowed the largest group (70%) of women with breast cancer (Er+ and Her2−) to be divided into seven subtypes. Whereas their overall 10-year survival rate is 75%, the new subtypes allow 15-year survival predictions from under 40% to over 80%.

Another new subtype definitely identifies Her2+ tumours, while another includes most of the ‘triple negative’ tumours.

The final subtype identifies tumours where inflammatory cells and lymphocytes are infiltrated. According to Caldas, this subset “is a very important one for us to have recognised” because it shows the role of the immune system in fighting cancer.

An easily injectable formulation of Roche’s breast cancer drug Herceptin has been shown to be as safe and effective as the intravenous version now available.

The new version of Herceptin (trastuzumab), available via subcutaneous (SC) injection, reduces the drug’s administration time from 30 to five minutes.

UK patients who are eligible for the SC formulation could be treated more rapidly, freeing up capacity in hospital chemotherapy facilities.

The HannaH trial compared Herceptin SC with Herceptin IV in 596 women with untreated HER2-positive early-stage breast cancer.

The study met its primary endpoint of ‘non-inferiority’ for pharmacokinetics and success in tumour eradication, and there were no new safety concerns.

Breast cancer is the most common cancer in the UK, with more than 48,000 newly diagnosed patients and 12,000 fatalities in 2008.

Herceptin is a targeted drug that blocks the function of HER2, a protein produced by a gene with cancer-causing potential. It uses the body’s immune system to destroy the tumour cells.

In 15% of women with breast cancer, increased quantities of the HER2 receptor are present on the tumour cells. HER2-positive breast cancer is associated with relatively poor survival rates.

Herceptin is indicated in Europe for the treatment of early-stage and metastatic breast cancer and metastatic gastric cancer. It is currently approved in an IV formulation only.

Herceptin SC uses a specialised technology to break down the skin barrier to drugs, enabling the subcutaneous injection of large volumes of medication.

Dr Mark Verrill, Consultant Medical Oncologist at Freeman Hospital, Newcastle Upon Tyne, commented: “The result of the HannaH trial is good news, particularly for patients. Herceptin is the standard of care, so the ability to deliver the drug in approximately five minutes without the need to secure intravenous access makes the treatment far more convenient.

“Aside from the benefit for patients, Herceptin SC has the potential to ease capacity at busy chemotherapy day units and may facilitate treatment close to home, resonating with the Cancer Reform Strategy.”

Roche is the world’s largest biotechnology firm, specialising in the development of personalised medicines for oncology, virology, inflammation, metabolism and CNS disorders.