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Tagged: cancer reasearch

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  • Stem cell study aims to improve prospects for lung cancer sufferers
  • Professor Sikora suggests that lung cancer is associated with poverty
  • Current therapies for lung cancer extend life by only a few months
  • Lung cancer kills more people than any other cancer

Lung cancer and cutting edge stem cell therapy

In 2015 a combined stem cell and gene therapy for lung cancer started its first clinical study in the UK. Professor Sam Janes of University College London, the study’s leader, said: “This will be the first UK cell therapy for lung cancer, and the biggest manufacturing of cells of its kind.” 

Dr Chris Watkins, director of translational research at the Medical Research Council, which is funding the study, said: “Lung cancer kills more men and women than any other cancer, and improving the outcome for patients with this terrible disease is one of the biggest challenges we face. This new therapy, which uses modified stem cells to target the tumour directly is truly at the cutting edge.”

 
Few studies
 
The use of stem cells for treating lung diseases has increasing appeal, but as yet, little is known about the effects of administering stem cell therapy to patients with lung diseases. Currently, there are only a small number of approved clinical studies in the US and Canada investigating cell therapy approaches for lung diseases. Patrick O’Brien a consultant obstetrician and gynaecologist at University College Hospital, London describes an initiative to create a national stem cell bank in the UK: 
 
       
 
Lung cancer
 
Lung cancer is the most common cancer worldwide, accounting for 1.8 million new cases and 1.6 million deaths in 2012. This year, an estimated 224,210 adults in the US, 40,000 in the UK, and 169,000 in India will be diagnosed with lung cancer, 90% of which are and caused by smoking. Of those diagnosed, 95% will die within ten years, although early stage lung cancer has a much better survival rate. Professor Karol Sikora, a world respected oncologist, and campaigner for better universal cancer treatment, suggests that lung cancer is associated with poverty:
 
    

Traditional therapies
 
Cell-gene therapy holds out new hope. “Lung cancer is very difficult to treat because the vast majority of patients are not diagnosed until the cancer has spread to other parts of the body. One therapy option for these patients is chemotherapy, but even if successful this treatment can normally only extend lives by a handful of months,” says JanesCurrent therapeutic strategies of chemotherapy, radiation therapy, and clinical studies with new-targeted therapies have only demonstrated, at best, extension in survival by a few months.
 
Innovative approach
 
“We aim to improve prospects for lung cancer patients by using a highly targeted therapy using stem cells, which have an innate tendency to home in on tumours when they’re injected into the body. Once there, they switch on a ‘kill’ pathway in the cancer cells, leaving healthy surrounding cells untouched,” says Janes. His study will test the treatment in human volunteers, firstly to check that the treatment is safe, and then in 56 lung cancer patients to see how effective the gene-cell therapy compares with standard care. Each patient in the study will receive three infusions comprised of billions of cells in parallel with chemotherapy.
 
Takeaways

A key advantage of Janes’ proposed treatment is that the cells do not have to be closely matched to a person’s tissue type or genetic profile. They are simply taken “off the shelf” from existing bone marrow supplies. This is because the cells have relatively few proteins on their surface, and do not induce an immune response in the recipient.
 
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  • Oncologists increasingly use targeted agents directed at molecular features of cancer cells
  • There is increased off label use of these new targeted agents without evidence to support the practice
  • A landmark study concludes that off label use of targeted agents show no benefit and should be discouraged
  • Professor Gabra, head of cancer at Imperial College, says more research is needed
 

Despite significant progress in cancer care over the past decade, there remain substantial challenges in the treatment of advanced cancers. This has increased off-label use of newer drugs based on molecular studies of tumours, largely without much evidence to support the practice.

A landmark clinical study, known as SHIVA, led by Christophe le Tourneau, a senior medical oncologist at the Institut Curie in Paris, raised expectations among both doctors and patients, because it is one of the first randomized studies to explore molecularly targeted agents applied outside their indicated use (off-label) among those with advanced cancers for whom standard therapies had failed.
 
Findings, published in Lancet Oncology, September 2015, concluded that, “off-label use of molecularly targeted agents should be discouraged,” since the study detected no improvement in survival rates when compared to treatments selected by clinicians that were not based on such sophisticated DNA profiling. 

What are the implications of the study’s negative findings for personalised medicine?

Christophe le Tourneau

In the videos below Le Tourneau describes the SHIVA trail and some of the challenges it faced.

   

   
    

The context

Cancer is a heterogeneous, complex, and challenging disease to treat. Tumours formerly categorized as a single entity on the basis of microscopic appearance are now known to be diverse in their molecular characteristics. Cancer chemotherapy is on an evolutionary path from non-specific cytotoxic drugs that damage both tumour and normal cells to targeted agents that are directed at unique molecular features of cancer cells, and aims to produce greater effectiveness with less toxicity.
 
Over the past decade our understanding of cancer and the basis of its treatment has been significantly changed by the advent of rapid and cheap DNA sequencing technology. The application of these sophisticated analytic techniques to arrive at a therapy for a particular cancer has been called “personalized oncology.” The idea of personalized cancer care based on molecular characteristics of the tumour promises to expand the boundaries of precision medicine. Numerous case reports and other observations have suggested that therapy targeted at molecular characteristics of a tumour can have significant beneficial effects.
 
These personalized therapeutic strategies have rendered traditional classifications of many cancers redundant, because they have advanced our understanding of the underlying biology and molecular mechanisms of specific cancers. Cancer is no longer considered a single disease entity, and is now being subdivided into molecular subtypes with dedicated targeted and chemotherapeutic strategies. The concept of using information from a patient's tumour to make therapeutic and treatment decisions has changed the landscapes of both cancer care and cancer research.

 

The SHIVA study

The SHIVA study, carried out at eight academic centres in France and conducted in 195 patients with metastatic cancer resistant to standard care, was a proof-of-concept, open-label, randomized controlled study. The patients were randomly assigned to receive either molecularly targeted agents (used off-label) chosen on the basis of the molecular profile of the tumour; or therapy based on the clinician's choice. The median follow-up period was 11.3 months. Findings showed a median progression free survival (PFS) of 2.3 months for patients receiving targeted therapy, versus 2.0 months for patients receiving therapy based on the clinician's choice.

"So far, no evidence from our randomised clinical trial supports the use of molecularly targeted agents outside their indications on the basis of tumour molecular profiling . . . . . Our findings suggest that off-label use of molecularly targeted agents outside their indications should be discouraged, and enrolment into clinical trials encouraged," says Le Tourneau and his colleagues.
 

More research required

Hani Gabra, Professor of Medical Oncology and Head of Cancer, Imperial College London says, "SHIVA is important because it is the first randomized study carried out in this complex area of matching drugs to genomic profiles of tumours. Despite the fact that the results are negative we should continue research in this area because personalised medicine is a relatively new area. One thing to note is that the molecularly targeted agents used in SHIVA were single agents, which could increase resistance and reduce the agent’s efficacy. In clinical practice we tend to use several targeted agents in combination in order to counteract drug resistance. SHIVA tested specific agents and specific targets, which resulted in disappointing findings. This doesn’t necessarily negate the overall strategy, but it does suggest that more research is necessary to test the overall strategy, and this might be more challenging.”
 

Takeaways

SHIVA is one of several on going and proposed studies aimed at defining the role of targeting sequencing of tumours in an endeavour to enhance therapy. The SHIVA study did not uncover any new positive evidence to help in the management of advanced cancers. Le Tourneau and his colleagues suggest further studies in a subset of patients that have tumours with molecular alterations in the chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Oncologists, while disappointed by SHIVA’S results, still hold out hope for their patients and advocate further studies.

 
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A new test, called ADNEX, reported in the British Medical Journal in October 2014 helps to identify different types and stages of ovarian cancer more accurately, which scientists claim will reduce the incidences of unnecessary surgeries. 
 
Accurate, simple and ready
The test, developed by an international team led by Imperial College London and KU Leuven, Belgium, is based on patient data, a simple blood test, and features that can be identified on an ultrasound scan. Doctors can use it simply by entering patient data into a smartphone app. It's highly accurate, and discriminates between benign and malignant tumours, and also identifies different types of malignant tumours.
 
Successful treatment depends on accurate diagnosis, and diagnosis of ovarian cancer can be challenging. According to Professor Tom Bourne, Department of Surgery and Cancer at Imperial College London, "The way we assess women with ovarian cysts for the presence of cancer and select treatment lacks accuracy. This new approach to classifying ovarian tumours can help doctors make the right management decisions, which will improve the outcome for women with cancer. It will also reduce the likelihood of women with all types of cysts having excessive or unnecessary treatment that may impact on their fertility.
 
Frequently misdiagnosed
The frequent misdiagnosis of ovarian cancer means that it often presents late when it has already metastasized. It's the most aggressive gynecological malady, with poor survival rates: only 40% survive beyond five years, and it can affect any woman.
 
The reason why early symptoms are difficult to detect is because inside the abdomen, the ovary has a lot of space to grow into before it starts to press onto other structures such as the uterus, bowel and bladder.
 
Early detection is key
All women should be on guard of the symptoms, which may be vague at first, and similar to other conditions, such as digestive disorders. The commonest symptoms are discomfort or pain in the lower abdomen or pelvis, and also there may be backache or a swelling felt.
 
There is a survival rate of up to 90% when ovarian cancer is caught early, compared with less than 30% if it is discovered in the later stages. 
 
Increasing incidence in younger women
Around 1 in 55 women will get ovarian cancer at some time in their life, and it is more common over the age of 40. Less than 1 in 20 ovary cancers occur in women younger than this. There are inherited factors involved in some cases, and research is underway to find out how best to screen women at increased risk of the disease. Since the mid-1970s, the incidence of ovarian cancer in women between 15 and 39 has increased by some 56%.
 
Takeaway
Currently, early detection, and rapid referral to a specialist gynaecological cancer unit is the key to transforming survival rates for ovarian cancer. Patients therefore have to rely on seeing a doctor, and being correctly diagnosed in time. 
 
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Cancer research and cancer treatment are evolving very rapidly. Built on a platform of intensive molecular research, the prognosis of cancer is beginning to be transformed. We have huge amounts of cancer information at our disposal. The challenge is how to translate these into the clinic and make cost effective treatments. 

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