Rarely does a single discovery have a fast and revolutionary impact on healthcare. But when geneticist Dr. Mary-Claire King, then professor of genetics and epidemiology at the University of California, Berkeley, discovered that a single gene was responsible for certain breast cancers, it changed the diagnosis and care of millions of women around the world.
It was 1990, and genetics was in the spotlight thanks to the launch of the Human Genome Project. Breast cancer rates had increased dramatically over the last decade due to improvements in screening with mammograms, but thousands of women still had no access to screening or diagnostics due to a lack of funding. What was needed was a new testing method – something Dr. King’s genetic discovery would inspire.
Such a direct link between genetic research and clinical practice was unprecedented in oncology. Scientists continue to investigate the genetic basis of disease, and with advances in technology, they are making new incremental discoveries every day. The journey these scientific discoveries take to the clinic is faster than ever, but it includes formidable obstacles. These challenges are spurring the development of tools to help researchers make further breakthroughs – and help practitioners assimilate the ever-growing supply of knowledge and data to find the best treatments for their patients. And they are sparking initiatives that bring together researchers, medical practitioners, patient advocates and policymakers to find new ways of harnessing this knowledge so patients can receive personalized treatment.
In fact, this kind of interdisciplinary thinking was behind Dr. King’s discovery, and it would lay the foundation for what we now call personalized medicine.
The breast cancer gene
Although breast cancer was not Dr. King’s area of expertise, she thought genetics could add something to the research going on at the time – which was focused on identifying a viral cause of cancer. The US National Cancer Institute was conducting a survey of 1,500 women with breast cancer as part of a study on oral contraceptives, so Dr. King asked them to add a question or two about close relatives with breast cancer. As she told the New York Times in an interview:
I asked a statistical question: ‘Does breast cancer cluster in families more than we’d expect by chance?’ The answer was yes. … But the gene was hypothetical. The best way to prove that it existed was to find it.
In 1990 Dr. King did just that, naming the gene BRCA, forBReast CAncer. It produces a protein – BRCA1 – that suppresses the formation of tumors by repairing damaged DNA. Mutations in the gene lead to changes in the protein that stop it from functioning properly, so breast tumors are able to grow.
Dr. King's lectureship with Cell Press and TnQ
Dr. Mary-Claire King will be presenting her cutting-edge research on the genetics of human disease in three cities across India in February as the 2017 Cell Press-TnQ India Distinguished Lecturer. The lectureship is a partnership between Elsevier’s Cell Press and the publishing technology and services company TnQ. The week-long lecture tour aims to bring the best in science each year to Indian students and scientists to stimulate exchange of ideas and inspire careers in scientific research.
From bench to bedside
Mutations in BRCA1 and a related gene – BRCA2 – account for up to 25 percent of hereditary breast cancers and 5 to 10 percent of all breast cancers, according to the National Cancer Institute. If a parent has a mutation in one of the genes, their child will have a one in two chance of inheriting that mutation. This will dramatically increase their risk of developing breast cancer; about 12 percent of women without a harmful BRCA1 mutation will develop breast cancer, compared to about 60 percent of women with a harmful mutation.
Being able to test for these mutations means women have choices – they can decide how to manage their risk. In 2013, actress and director Angelina Jolie published an article about her decision to have a double mastectomy after a harmful mutation in her BRCA1 gene was identified. She wrote in the New York Times:
Cancer is still a word that strikes fear into people’s hearts, producing a deep sense of powerlessness. But today it is possible to find out through a blood test whether you are highly susceptible to breast and ovarian cancer, and then take action.
But more widely, the genetic causes of cancer are not so clear-cut. Although there is a strong link between certain harmful mutations in BRCA1 and developing breast cancer, there are thousands of possible mutations in this and other genes that can affect a person’s risk of disease. Academic clinician and prostate cancer surgeon Dr. David Neal, Senior VP of Global Academic Research at Elsevier and Professor of Surgical Oncology at the University of Oxford, explained the complexity:
We inherit not a single gene mutation that causes disease but hundreds of slight genetic variations that add together to cause it. This results in a genetic predisposition to a certain disease. Although two people may have breast cancer, the genetic causes and resulting tumors could be very different. Breast cancer is not a single disease; it’s probably about 20. Treating them all in the same way with same drugs is ineffective.
This is where the idea of precision medicine comes in. With our growing knowledge of the genetics of diseases like cancer, it is possible to characterize a person’s disease and determine their best course of treatment.
Shooting for the moon
In March 2016 a phase 3 clinical trial involving 257 women with a certain type of breast cancer – HER2-positive – showed that treating them with a combination of drugs before surgery could lead to their tumors disappearing.
As the journey from cancer research to treatment accelerates, so does the volume of data that can inform further research and treatment. At Elsevier, we’re developing tools to help researchers make further breakthroughs, and help practitioners find the best treatments for their patients. For stories about people and projects empowered by knowledge, we invite you to visit Empowering Knowledge.
In the trial, called EPHOS B, Cancer Research UK scientists split participants into three groups: the first group received no treatment before surgery, the second received the antibody treatment Herceptin (trastuzumab) and the third received a combination of Herceptin and the drug lapatinib.
In seven of the 66 women who received the combination therapy, the tumors disappeared. With a further 11, only minute traces of the cancer remained. It is early, but this could mean that for certain types of HER2-positive breast cancer, women could have this combination treatment followed by surgery, without the need for chemotherapy.
The key to providing this sort of personalized treatment is understanding the disease that needs to be treated. This is the theory behind the Cancer Moonshot Initiative – a US program that aims to accelerate cancer research. Dr. Neal explained:
Because every tumor is different, in a way each individual with cancer has a rare disease. Precision medicine aims to tackle this. You can take a biopsy of a person’s tumor, extract the DNA and fragment it and then sequence it. If you then compare this with the individual’s normal genome you can find out where mutations have occurred. The idea is that this will give doctors the information they need to prescribe the ideal treatment for that patient’s disease.
Dealing with data
To succeed, the initiative will need huge amounts of genomic data, which will require institutions to collaborate and share information. As Dr. Neal explained:
Scientists won’t be able to study individual cancers from any one particular hospital; there won’t be enough patients. What’s needed is an electronic platform to link clinical, genomic and proteomic data and pull data from different hospitals and repositories. This is something we are working on at Elsevier.
In addition to developing platforms for data sharing, Elsevier is analyzing global cancer research to highlight the collaborations that are working and those that are proving challenging. The report will give the Cancer Moonshot Initiative leaders the information they need to allocate funding and make strategic decisions. Project lead Dr. Brad Fenwick, Elsevier’s Senior VP for Global Alliances, commented:
Because cancer is a large, diverse and continually evolving, it’s extremely challenging to figure out where the research opportunities and challenges are. For the Cancer Moonshot Initiative, we’ll provide data on the current state of cancer research and the impact from the large data sets and research collaborations. Ultimately the report will provide a pathway to the most promising outcomes that will affect the greatest number of people.
Assuming the Cancer Moonshot Initiative accelerates cancer research output, this would result in a huge influx of new research data, clinical trial results and medical knowledge. In 1950, it took 10 years for all the world's medical knowledge to double. It's projected that the entire world's medical knowledge will double every 73 days by 2020 – and this provides a challenge. Elsevier’s Chief Medical Officer Dr. Peter Edelstein explained:
It is no more possible for even the most intelligent physician with all day available to keep up with the current evidence and provide the best care to every patient without technology than it is to learn every single word in the English language and never have to look anything up.
Patients with power
But it’s not just healthcare professionals who will need to navigate the information; patients will be increasingly involved in their own treatment decisions. As author of the book Own Your Cancer: A Take-Charge Guide for the Recently Diagnosed & Those Who Love Them, Dr. Edelstein is a proponent of the patient as a provider:
Statistically, all healthcare takes place away from doctors and nurses and pharmacists. It's in your home. It's at work. It's at dinner. It's at the movies. You're on vacation. In the United States, 50 percent of patients do not take the prescription medications as prescribed – this is associated with 125,000 deaths a year, 10 percent of hospitalizations and $289 billion in waste. Clearly, we can start with doctors and nurses, but this will have minimal impact on public health unless the patient is engaged.
In order for today’s research to be transformed into tomorrow’s treatment, patients will need to understand and embrace it. Cancer can be very overwhelming and seem too complex for many patients and their families to understand; genomics only increases that complexity. So how can we overcome this last obstacle on the journey from bench to bedside? Dr. Edelstein describes the work of his patient engagement team:
They take current evidence-based knowledge and work with experts to put it into the right language, empowering patients to use the latest research to inform their decisions.
With groundbreaking cancer research and clinical trials alongside major initiatives like the Cancer Moonshot, cancer research has never been so energized. As technology continues to develop, we will see better molecular imaging, less invasive surgery and more targeted drugs. If patients are empowered to understand and apply evidence-based information to their own treatment decisions, the path from basic research to clinical application will be shorter than ever.
How clinical solutions work
Elsevier’s information solutions help healthcare providers navigate the vast field of information and evidence to make decisions about patient care. Dr. Edelstein used an analogy to explain how they work:
In a car, you have a seat belt that can save you, but only if you use it. You also have an air bag that you don’t need to activate. Through technology, we can enable healthcare professionals to ‘pull’ current evidence-based information they need – the seatbelt – or we can ‘push’ information to them – the airbag. Elsevier’s technology solutions like Clinical Key aim to do this.
Source: Elsevier Connect