Category Archives: Genetic Medicine

When the UK Life Sciences Champion Sir John Bell recently highlighted the need to create new industries within life sciences, Carina Healy immediately saw the potential for Scotland.

When the UK Life Sciences Champion Sir John Bell recently highlighted the need to create new industries within life sciences, Carina Healy immediately saw the potential for Scotland.

Sir John, speaking at the Medicines and Healthcare Products Regulatory Agency, identified genomics, digital health and early diagnosis as three areas where the UK could develop new industries and remain a world leader in life sciences.

Healy, a partner and life sciences specialist with international legal firm CMS, says: These areas play into what we do well in Scotland and present very big opportunities. Healy goes on to explain these new industries and the potential they hold for Scotland.

Genomics using genotyping to inform how patients are treated is closely linked to precision or stratified medicine, where Scotland is already excelling.

Precision medicine allows doctors to tailor treatments to each patients specific needs, which can save lives, avoid unpleasant side-effects caused by unsuitable treatments and save the NHS money.

Scotland has great expertise in this area, with world-class academic research and cutting-edge companies developing new treatments to benefit the NHS. This is backed by innovative initiatives such as the Stratified Medicine Scotland Innovation Centre based at the Queen Elizabeth University Hospital (QEUH) in Glasgow, which brings together specialists from across academia, industry and the NHS.

One challenge facing this new industry is how to use the wealth of genetic data now available to inform medical treatment. Although genetic testing is getting increasingly more affordable, further research is needed to link that genetic data to specific diseases and treatment options.

As Healy explains: The technology is there, but it doesnt tell you much yet. However, in areas like breast cancer, the use of the BRCA and HER-2 biomarkers is well-established and gives a clear indication of whether a certain class of patient is at risk or will respond to a specific drug like Herceptin.

Healy says that, in the hospital of the future, an individuals genetic profile is likely to be available in the same way as access to, for example, an individuals blood type. She says: Were still quite far away, but weve decoded the genome and can do it cost-effectively. With further research we will be able to know how to make best use of this data to deliver more effective health care for individual patients.

A UK government science and innovation audit of precision medicine in Scotland this year, led by the University of Glasgow, highlighted the significant assets Scotland has in this field and their potential. It suggested the effective use of electronic health records could drive collaboration and help turn academic research and innovation into better clinical practice.

Healy says the universitys bid for a Strength in Places grant to create a Living Laboratory for precision medicine at QEUH is an excellent example of how Scotland can bridge the gap between genomics research and patient benefit.

Digital health, which uses software, mobile apps and digital technology for health purposes, is an area where Healy thinks Scotland has work to do but has all the key skills in place to make real progress.

We have real strength in informatics, data science and AI in our academic research institutions, she says. Although we need to integrate those sectors better with life sciences and healthcare. The potential is there to build real capacity and deliver tangible patient benefits.

In terms of digital health, this means making healthcare more efficient through use of digital technology, and improving the patient-facing offering.

Scotland has great assets in the IT sector generally, from Silicon Glen to the burgeoning technology scene in Edinburgh. The capital is set to receive further investment in technology infrastructure as part of the 1.3 billion Edinburgh City Region Deal, which will focus on data-driven innovation and help boost Scotlands existing capabilities.

The key to realising Scotlands potential in the new digital health industry will be in linking the countrys digital expertise with its life sciences expertise to create new solutions. Work to link Scotlands technology and life sciences industries has already begun. Exscientia, a company founded in Dundee, has been at the forefront of using digital technology to improve the drug discovery process, resulting in several collaborations this year with big-name drugs companies.

Further collaboration between the two industries will be supported by Glasgows Industrial Centre for Artificial Intelligence Research in Digital Diagnostics iCAIRD which involves 15 partners from across academia, industry and the NHS.

Healy stresses that although collaboration between private companies and the NHS has huge potential benefits, these collaborations must be structured correctly. It is especially important to address ethical and legal issues in accessing and managing patients data.

The collaboration between Googles DeepMind and Londons Royal Free Hospital, which involved the transfer of personal data of 1.6 million patients, was an example of a collaboration that was not structured correctly and was found to be in breach of data protection laws. Healy says: This erodes public trust in these types of initiatives, despite the very obvious benefits in healthcare treatment that can be generated.

Despite this setback, DeepMinds Streams app is now in use at the Royal Free Hospital and has been shown to enable consultants to treat acute kidney injury faster, potentially saving the NHS on average 2,000 per patient and saving consultants up to two hours per day.

The great advantage for Scotland is that we have one NHS. We can access data sources more easily and we can pool it more effectively, says Healy. However, practices can vary across different hospitals and trusts, and clear central guidance would be helpful to ensure data is used both ethically and effectively.

There are also issues around data quality as it is, of course, collected for clinical purposes, not for research or for training artificial intelligence systems.

The ultimate goal is to pool data for patient benefit, and to structure collaborations between private companies and the NHS carefully so personal data is managed appropriately.

There are also potential societal and political issues around ensuring all patients can benefit from digital health initiatives, for example in areas like GP surgery triage. Systems such as Babylon and DrDoctor allow patients remote access to GP services, but often benefit specific groups rather than the whole population.

Younger, more IT-literate patients who have a specific issue but are generally healthier tend to use systems like this, while older, less IT-savvy patients with chronic conditions still go to GP surgeries, says Healy. So GP surgeries are left with patients who need more care and time, but the funding per patient is the same. The digital health gap between different generations will close over time, but it is still quite wide now.

Overall, Healy notes, the message is that digital health offers huge opportunities in Scotland:

We need to encourage more health tech businesses to work with the NHS in Scotland and get more entrepreneurs looking at this area. There are big opportunities for new entrants.

In the third new life sciences industry, early diagnostics, Healy also sees a huge area of unmet need and opportunity in Scotland. She cites image recognition AI, where, for example, training an artificial intelligence system using large numbers of CT scans can mean tumours are spotted more quickly and accurately than using a surgeons eye, leading to earlier diagnosis, which in turn means more successful treatment for patients and potential savings for the NHS.

Scottish-based companies, including Canon Medical Research Europe, are exploring how technology such as AI can help with early diagnosis. Canons research, supported by the Scottish Funding Council, is looking for innovative ways to diagnose and measure mesothelioma tumours, which are particularly difficult to measure and treat.

Collaborations between Scottish companies and the NHS which capitalise on the organisations pool of health data will be a big boost to research and development of early diagnostics, particularly with the help of AI.

Although Healy recognises the challenges in collaborating on such projects, she is positive about the future: It can still be hard to break down NHS silos and work through its contracting processes. However, Scotlands strength is underpinned by excellent collaboration between the NHS, academia and industry. You can see it working in projects like iCAIRD and the QEUHs Clinical Innovation Zone.

Healy sees this as a good reason for Scotland to be positive about its life sciences industry and its opportunity to make the most of Sir Johns three new industries genomics, digital health and early diagnostics. It all comes back to that strong, deep collaboration. We need to build on that and keep selling Scotlands strengths to a wider global marketplace.

Our academic base is really strong, we have one NHS with very good electronic health records and the ability of industry to collaborate across different academic and NHS bodies to deliver positive patient outcomes.

Find out more at CMS.

Read more here:
CMS on on how life sciences advancements are improving patient care - The Scotsman

In a recent issue, TIME rounded up 12 medical innovations that will transform "medicine at a remarkable pace" over the next decade.

Innovator: United Parcel Service CEO David Abney

Several operations have recently set their sights on delivering medical supplies via drone, and a big name in the effort is United Parcel Service (UPS), led by CEO David Abney. Earlier this month, the Federal Aviation Administration (FAA) granted UPS approval to expand its Flight Forward program, which uses drones to deliver medical samples and medications between hospitals. But UPS isn't the only name in the game. Wing, a division of Google's parent company Alphabet, also received FAA approval to make drone deliveries for Walgreens and FedEx. In Africa, the startup Zipline already delivers medical supplies to villages in Ghana and Rwanda.

Innovator: Christine Lemke, co-founder and president of Evidation

Tens of millions of people use wearables that track their health data. Now, data firms are looking into creating anonymous, searchable databases that aggregate data from wearables that researchers can use for studies. For instance, the data firm Evidation, co-founded by Christine Lemke, has developed a tool that aggregates the health information of three million volunteers for use in peer-reviewed medical studies.

Innovator: Doug Melton, co-founder of Semma Therapeutics

Ten years ago Doug Melton, a Harvard biologist, started researching how stem cells could be used to cure diabetes. In his research, Melton found that stem cells can create replacement beta cells that produce insulin. In 2014, he co-founded Semma Therapeutics and developed a small implant that holds millions of the replacement beta cells and blocks immune cells. "If it works in people as well as it does in animals, it's possible that people will not be diabetic" when treated with the implant, Melton said.

Innovator: Abasi Ene-Obong, founder of 54gene

While white people are in the minority globally, they make up almost 80% of subjects in human-genome research. To address the discrepancy, Abasi Ene-Obong founded a startup called 54gene that collects genetic data from volunteers across Africa to diversify drug research and development. "If [African people] are part of the pathway for drug creation, then maybe we can also become part of the pathway to get these drugs into Africa," Ene-Obong said.

Innovator: Sean Parker, founder of the Parker Institute for Cancer Immunotherapy

The Parker Institute for Cancer Immunotherapy, which is a network of top research institutions including the MD Anderson Cancer Center and Memorial Sloan Kettering, aims to identify and break down obstacles to innovation in cancer research. To help accelerate the research process, the network will accept approvals from the Institutional Review Board of any of the participating institutions in order to "get major clinical trials off the ground in weeks rather than years," according to Sean Parker, founder of the institute and former president of Facebook. The institute has brought 11 projects to clinical trials since it was founded in 2016.

Innovator: Thomas Reardon, CEO and co-founder of CTRL-Labs

CTRL-Labs has developed a wearable device, called the CTRL-kit, which wearers can control with their minds. When the person wearing the device thinks about a movement, the device detects the electrical impulses that travel from their brain to their hand. The device holds the potential to allow patients recovering from debilitating conditions to access new forms of rehabilitation, according to Thomas Reardon, CEO and co-founder of CTRL-Labs.

Innovator: Jonathan Rothberg, founder and CEO of Butterfly Network

To close the gap in access to medical imaging, Butterfly iQ developed a handheld ultrasound device. The device costs $2,000 compared to the $100,000 cost of a machine in a hospital. While the device isn't as precise as hospital machines, Jonathan Rothberg, founder and CEO of Butterfly Network, said the goal is that the devices will make scanning more routine.

Innovator: Shravya Shetty, senior staff software engineer at Google

Lung cancer is usually diagnosed in its later stages, TIME reports, and early screening can lead to bad results, such as misdiagnosis. Shravya Shetty, senior staff software engineer at Google, and her team at Google Health built an artificial intelligence (AI) system that detected 5% more lung cancer cases and had 11% fewer false positives than a group of radiologists. While the technology isn't yet where it should be, Shetty said it could have a big impact in the future.

Innovator: Joanna Shields, CEO of BenevolentAI

More than two million peer-reviewed research papers are published each year, which is too many for scientists to read themselves, TIME reports. To help science keep up, BenevolentAI created an algorithm that can read through the research papers to detect previously overlooked discoveries related to disease, drugs, and genes.

Innovator: Sean Slovenski, SVP & president, Walmart Health & Wellness

More retailers are entering the health care market, and a company at the forefront of this movement is Walmart, according to TIME. Leading Walmart's push into health care is Sean Slovenski, a former Humana executive who now heads Walmart Health & Wellness. Tn September, Walmart opened its first Health Center, where customers can get primary care, vision tests, and lab work, according to TIME. The potential is "huge," TIME reports, but so are the possible repercussions. For instance, health care providers might struggle to adjust to retailers' lower prices, according to TIME.

Innovator: Charles Taylor, founder of HeartFlow

A lot of patients with suspected heart problems have to undergo invasive procedures to diagnose blocked arteries. To make the process less invasive, Charles Taylor founded HeartFlow to create personalized 3-D heart models that doctors can use to diagnose patients, allowing patients to avoid invasive procedures during the diagnosis process.

Innovator: Isabel Van de Keere, founder of Immersive Rehab

In 2010, Isabel Van de Keere was left with a cervical spine injury and severe vertigo after a work accident. After years of neurological rehab, de Keere founded Immersive Rehab, a startup that aims to incorporate virtual reality into neurological rehab. Virtual reality gives patients access to a variety of exercises, making rehab less monotonous and frustrating for patients (Park, Becker's Health IT & CIO Report, 10/29; TIME, 10/25).

See the article here:
What health care will look like in 10 years, according to TIME - The Daily Briefing

The big news story for the cancer community this week has been the setting up of a new transatlantic research alliance with the ambition to develop new strategies and technologies to detect cancer at its earliest stage.

Those involved in this initiative, including Cancer Research UK (CRUK) believe thatearly detection is essential to help more people beat cancer a patients chance of surviving their disease improves dramatically when cancer is found and treated earlier.

Early diagnosis is, of course, a wish of the brain tumour community. All too often we hear of patients who have had to wait many months, with many visits to the GP before establishing the cause of their symptoms. However, we must not forget that earlier diagnosis may bring relief but there remains a lack of treatments. There is still no cure for many brain tumour patients

In the Report of the Task and Finish Working Group on Brain Tumour Research released February 2018 this was summed up perfectly by brain tumour activist Peter Realf who said While I endorse the need to improve earlier diagnosis, this alone without a cure will simply mean that patients face a longer walk to the grave.

In Texas there is work on in vitro blood brain barrier (BBB) models to equate their strengths and weaknesses. In-vitro means in the glass so these models are constructed with microorganisms, cells, or biological molecules outside their normal biological context e.g. in the petri dish or test tube. Work in this arena has previously been under taken at our University of Portsmouth centre. A combinatorial approach of in vitro BBB models and in-vivo (within the living) methods is thought to be key to the development of CNS therapeutics (medicines) with improved pharmacokinetic (the movement refers to the movement of drug into, though, and out of the body) properties and better BBB penetrability.

Most cancers kill because tumour cells spread, or metastasise, beyond the primary site, for example breast, to invade other organs, brain being one. Now, a University of Southern California (USC), study has found that circulating tumour cells in the blood target a particular organ and this knowledge may enable the development of treatments to prevent the spread of these metastatic cancers.

Analysis of these cells identified regulator genes and proteins within the cells that apparently directed the cancers spread to the brain. The team were therefore able to predict that a patients breast cancer cells would eventually migrate to the brain.

Assistant professor of stem cell and regenerative medicine at the Keck School of Medicine at USC, Min Yu, also discovered that a protein on the surface of these brain-targeting tumour cells helps them to breech the blood brain barrier and lodge in brain tissue, while another protein inside the cells shield them from the brains immune response, enabling them to grow there.

We can imagine someday using the information carried by circulating tumour cells to improve the detection, monitoring and treatment of the spreading cancers, Yu said.

A compound effective in killing chemotherapy-resistant glioblastoma-initiating cells (GICs) has been identified, raising hopes of producing drugs capable of eradicating refractory tumours (tumours that dont respond to treatment) with low toxicity.

As we are all too aware, despite longstanding and earnest endeavours to develop new remedies, the prognosis of most glioblastoma patients undergoing chemotherapies and radiotherapies remains poor with a median survival period of approximately 15 months.

One of the reasons for this is the lack of methods to eradicate its cancer stem cells, or glioblastoma-initiating cells (GICs), that demonstrate tumourigenicity (ability to form tumours) and resistance to chemotherapies and radiotherapies.

This study successfully cultured human GICs resistant to temozolomide (TMZ), the gold standard chemotherapy drug used for treating glioblastoma.

Then a high-throughput drug screening was conducted to identify a compound that could specifically kill or inflict damage to GICs, but not normal cells such as neural stem cells and astrocytes.

Compound 10580 was successfully identified as being capable of killing or inflicting damages to GICs whilst at the same time exhibiting no visible toxicity

"Compound 10580 is a promising candidate for developing drugs against glioblastoma and other recurring cancerssaid Toru Kondo of Hokkaido University's Institute for Genetic Medicine who led the study.

What is also interesting here is the collaborative nature of the study group with Hokkaido University, working alongside FUJIFILM Corporation and the National Institute of Advanced Industrial Science and Technology (AIST).

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Weekly pick of Neuroscience news from around the world - Brain Tumour Research

The National Institutes of Health and the Bill and Melinda Gates Foundation will together invest at least $200 million over the next four years to develop gene-based cures for sickle cell disease and HIV with an attribute even rarer in the world of genetic medicine than efficacy, the groups announced on Wednesday: The cures, they vowed, will be affordable and available in the resource-poor countries hit hardest by the two diseases, particularly in Africa.

The effort reflects growing concerns that scientific advances in genetic medicine, both traditional gene therapies and genome-editing approaches such as CRISPR, are and will continue to be prohibitively expensive and therefore beyond the reach of the vast majority of patients. Spark Therapeutics Luxturna, a gene therapy for a rare form of blindness, costs $425,000 per eye, for instance, and genetically engineered T cells (CAR-Ts) to treat some blood cancers cost about the same.

With CRISPR-based treatments already being tested in clinical trials for sickle cell disease, the blood disorder beta thalassemia, and another form of blindness, and with additional CRISPR treatments in development, scientists, ethicists, and health policy experts have grown increasingly concerned that the divide between haves and have-nots will grow ever-wider.

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Gene-based treatments are largely inaccessible to most of the world by virtue of the complexity and cost of treatment requirements, which currently limit their administration to hospitals in wealthy countries, the NIH said in a statement. To help right that, its collaboration with the Gates Foundation aims to develop curative therapies that can be delivered safely, effectively and affordably in low-resource settings.

Scientists whose research focuses on gene-based cures welcomed the infusion of funding and the recognition that genetic cures are on track to be unaffordable to the majority of patients. But they noted one irony. The most effective sickle cell drug, hydroxyurea, has hardly even been studied in sub-Saharan Africa, let alone made widely available. Yet a 2019 study found that giving children the drug cut their death rate by two-thirds and halved the pain crises that are common in sickle cell disease, caused by misshapen red blood cells that cannot flow through blood vessels.

The NIH-Gates collaboration is tremendously exciting and has the potential to have a great impact on sickle cell disease in sub-Saharan Africa, said Dr. Vijay Sankaran of the Dana-Farber/Boston Childrens Cancer and Blood Disorders Center, who has done pioneering research on genetic cures for the disease. But my hesitation is that even the inexpensive therapies we have today, such as hydroxyurea, are largely unavailable there. The question is, how do we best approach this disease, with therapies that are working today or with genetic therapies that might work?

The same concerns surround HIV. Very inexpensive less than $100 per year in the U.S. antiretroviral drugs can keep the virus in check, but only 67% of HIV-positive adults and 62% of HIV-positive in children in east and southern Africa are estimated to be on antiretroviral treatment.

The new collaboration aims to move gene-based cures into clinical trials in the U.S. and countries in sub-Saharan Africa within the next seven to 10 years, and to eventually make such treatments available in areas hardest hit by sickle cell disease and HIV/AIDS. The idea is to focus on access, scalability, and affordability to make sure everybody, everywhere has the opportunity to be cured, not just those in high-income countries, NIH Director Francis Collins said in a statement. We aim to go big or go home. But the challenge is enormous, he told reporters on Wednesday: Im not going to lie. This is a bold goal.

An estimated 95% of the 38 million people with HIV live in the developing world, with 67% in sub-Saharan Africa. Up to 90% of children with sickle cell disease in low-income countries die before they are 5 years old. In the U.S., the life expectancy for people with sickle cell disease is in the low 40s.

The NIH and the Gates Foundation will fund research to identify potential gene-based cures for sickle cell and HIV, and also work with groups in Africa to test those cures in clinical trials.

The science of genetic cures for both diseases is within reach, experts say. CRISPR Therapeutics and Vertex (VRTX) are already running a clinical trial for sickle cell disease, using the CRISPR genome editor to do an end-run around the disease-causing mutation in the hemoglobin gene: The therapy releases the brake on red blood cells production of fetal hemoglobin, whose production shuts off in infancy but which does not have the sickling damage of adult hemoglobin.

Developing effective, safe genetic cures for sickle cell and HIV would be only a first step, however. As currently conceived, such therapies require advanced medical facilities to draw blood from patients, alter their cells genomes in a lab, give the patients chemotherapy to kill diseased blood-making cells, and then perform whats essentially a bone marrow transplant, followed by monitoring patients in a hospital for days to prevent infection and provide intensive medical support, said Dr. Dan Bauer, a sickle cell expert at Boston Childrens.

He called the NIH-Gates effort terrific, but cautioned that delivering advanced gene therapies requires tremendous effort, extended hospitalization, and large supplies of blood products. All of those requirements mean that even if a CRISPR-based cure for sickle cell disease or HIV were provided at cost, there will still be barriers to access.

Recognizing that, Collins said, a genetic cure would have to be given directly into patients (in vivo), presumably through an infusion, rather than by treating blood or other cells removed from patients and genetically transformed in a lab (ex vivo). That could avoid the resources needed for and the complications that can occur with ex vivo therapies, said Sankaran, who has discussed the approach with Gates officials.

This story has been updated with additional comments.

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NIH, Gates Foundation aim to bring genetic cures to the poor - STAT

Abstract / Synopsis:

There is some controversy over whether every single woman with breast cancer shold have genetic testing, or whether it should only those who have some personal or family history that would suggest their breast cancer may be linked to an inherited mutation. There are also tests of the tumor that look for somatic mutations. Here, we explore the arguments and options.

Recently, ONCOLOGY spoke with primary study author Dr. Allison W. Kurian about a new breast cancer study that analyzed the mutations present in breast tumors, and about emerging targeted therapy options. Dr. Kurian is associate professor of medicine and oncology and health research and policy at the Stanford University Medical Center in California. Her clinical practice focuses on women at high risk for developing breast and gynecologic tumors and treating women who are diagnosed with breast cancer. She is also director of the Stanford Womens Clinical Cancer Genetics Program.

Q: First, what are the standard genetic tests the vast majority of women who are diagnosed with breast cancer undergo or should undergo? Do these tests assay for both somatic and germline mutations?

Dr. Kurian: This is a great question. I would say the answer is still specific to the kind or stage of breast cancer a woman has. A great number of women now qualify under existing guidelines for testing for inherited genetic mutations. Examples of that would be testing for the BRCA1 and BRCA2 mutations. There is some controversy over whether that should be every single woman with breast cancer or only those who have some personal or family history that would suggest their breast cancer may be linked to an inherited mutation. There are also tests of the tumor that look for somatic mutations. Right now, somatic mutation tests are typically reserved for those women with advanced metastatic disease, but there are some early gene expression tests such as the Oncotype DX (21-gene test) we often use.

Q: You see women who are, compared to the general population of women, at higher risk for breast and ovarian cancers. How do these women typically find a clinician such as yourself? Do they know they carry a cancer susceptibility mutation because someone in their family has been diagnosed with breast cancer or a gynecologic cancer?

Dr. Kurian: The patients I see tend to be a mix. At the Stanford Womens Clinical Cancer Genetics Program, which is similar to many cancer genetics clinics around the country, we see people because they are referred for their own personal cancer diagnosis. This is often because they had a breast cancer diagnosis at a young age or a breast cancer diagnosis with family history or ovarian cancer. For these patients, we might do a genetic test and find an inherited genetic mutation. If we do, then we might ask them to reach out to their relatives and have them tested. Other times, maybe the relative with cancer has been tested somewhere else and her unaffected relative might find us for genetic testing and recommendations about how to manage cancer risk.

Q: You and your colleagues recently conducted this study survey examining genetic testing among women diagnosed with breast or ovarian cancers.[1] Can you tell us about the study design and what prompted you to do this?

Dr. Kurian: Absolutely. The study design is based in the largest and highest-quality population-based cancer registry in the United States, which is the SEER [Surveillance, Epidemiology, and End Results] registry. The SEER registry covers about one-third of the US population in terms of recording (cancer diagnosis), survival, and other outcomes of patients. We were very interested in looking across the whole population, so not just people being seen at academic centers like Stanford University but everyone, and understanding what happened in terms of genetic testing. What we were able to do was to look at the large populations of the states of California and Georgia, which together add up to 50 million people. We were able to use the SEER registry from both states that covers the whole population. This means that we did not leave anyone out. We then were able to do a data linkage, which was really exciting and innovative. We worked together with the four major testing laboratories that provide genetic testing to link the genetic data to the cancer registry data. Thus, we were able to learn a great deal about who actually gets tested and what was found.

Q: What did your study find that was particularly surprising to you?

Dr. Kurian: The study had a number of interesting results. Probably the most striking one was that only less than one-third of patients with ovarian cancer ever got genetic testing.[1] For more than 10 years, there have been guidelines from a number of different societies, from cancer societies to obstetrics and gynecology societies, that say everyone with (the standard kind of) ovarian cancerhigh-grade serous ovarian cancershould get genetic testing. So, to see that it was fewer than 30% was really concerning in terms of under-testing. Now, our analysis was based on data gathered from 2013 to 2014 and this figure may have improved in more recent years. Those years, however, were times when it was very clear that everyone needed to be tested. I think that under-testing is of concern. We did see that was more of a problem in African American women and women without insurance. So, there are certainly issues there that we saw in this study.

Q: So about this under-testing, are there potentially obvious reasons for this and is it something that you and your colleagues are looking at further?

Dr. Kurian: I think its an important question, and I dont know exactly why there was this under-testing trend. When we see a difference of disparity by ethnic characteristics, insurance, and socioeconomic status, we think about access barriers in terms of whether some people are getting less effective care or have clinicians who maybe dont understand that they need to refer them for genetic testing. Or could this be a situation in which patients have other barriers? They may be dealing with a lot other than cancer treatment and doing one more thing like a genetic test is just too much. It was interesting that we didnt see these problems with breast cancer, only with ovarian cancer. It does suggest a particular area to target. We are actually in the process of applying for funding to do a much more focused study of ovarian cancer patients to try to understand why this might be and how we might fix it.

Q: Anything else in general to add on this topic, including any advice for clinicians who see patients with breast and ovarian cancer, and anything else on the specific vulnerable populations that you identified?

Dr. Kurian: Ovarian cancer patients need genetic testing, period. This is straightforward and its something where again, as we see that there seems to be under-testing in women with less insurance and women of African American ethnicity, there needs to be particular care that those patients are appropriately counseled and tested and referred to specialists and geneticists as needed.

Q: Could you talk about the growing therapeutic options specific for breast cancer based on genetic mutations that have been uncovered? Are there now novel targets that are being explored in clinical trials or that may be tested in clinical trials soon?

Dr. Kurian: Yes. Its been an exciting several years in this breast cancer therapeutics space. When I started in the field in 2002, we really didnt have any targeted therapy related to inherited gene mutations. Over the last several years, we have seen the development of PARP [poly (ADP-ribose) polymerase] inhibitors, which are drugs that can be very effective in treating ovarian cancer in women who have an inherited genetic mutation. These drugs also sometimes work in women who dont have a genetic mutation, but they seem to be particularly effective if women have an inherited genetic mutation. More recently, PARP inhibitors have also been approved for treatment of breast cancer in women who have an inherited genetic mutation. Its more relevant than ever before to understand what the genetic testing results are in terms of guiding treatment of cancer. And there are a number of other clinical trials ongoing also focused on these questions. Some of these clinical trials are combining PARP inhibitors with immunotherapy, which were excited to learn more about and seem promising.

Q: Anything else you would like to mention about either therapy or genetic testing for breast cancer patients?

Dr. Kurian: This is an interesting and exciting time to live in, in terms of the practice of medicine and oncology. A lot of the promise of genetics and genomics is just being unlocked. I think theres great importance both in pursuing the bench science and clinical science side of things in terms of clinical trials and understanding which mutations might be targetable. But there is also a huge need to work on the population sciences and implementation side, which is really thinking about how do we use genetic testing, how do we make sure people get this testing, and how do we make sure that the results are acted on and managed appropriately.

Key Question

For this type of genetic testing, are there any hurdles logistically for these women as far as getting the testing done?

Dr. Kurian: It has been interesting as the cost of genetic testing has fallen dramatically over the last 5 or 6 years. It used to be that to get the most clinically relevant genes, BRCA1 and BRCA2, tested could cost more than $3,000. It really was difficult for a number of people, and although insurance covered it, insurance companies were relatively stringent about whom they would cover to get the testing done. Now, however, it is inexpensive. The testing has dropped down to a cost of maybe $200 out of pocket to get a large panel of genes tested if insurance does not pay. I still wish it were $5 or no cost, but $200 becomes much more attainable and often insurance does pay. So, the barriers in terms of costs are much less than they used to be. A lot of the time, however, we have barriers related to what is understood by the clinicians who are seeing these patients and whether it is realized that it is important to refer women who have early-onset breast cancer, breast cancer with a family history, or ovarian cancers to have appropriate genetic counseling and testing.

Disclosure: Dr. Kurian has received research funding from Myriad Genetics.

PERSPECTIVE

Important Research, Next Steps

Banu Arun, MD

The authors of this study have provided us with an important snapshot of the frequency of genetic testing in a population-based cohort of breast and ovarian cancer patients, including a subpopulation analysis in the United States. This study provides important information, helping to build a foundation of the current state of genetic testing in these cancer patients in order for clinicians and geneticists to identify the issues and gaps with regard to genetic testing. The study showed that the frequency of genetic testing is fairly low for both breast and ovarian cancer patients and is even lower for those women without insurance. The work also underscored the racial disparity that exists as the frequency black and Hispanic women who underwent genetic testing was lower compared to the frequency of white women that were tested. This study is a step towards first identifying the populations that are underserved when it comes to genetic testing and second, implementing strategies to improve the frequency of genetic testing in the clinic. While the study focused on data from populations in Georgia and California, future studies should analyze whether testing patterns are similar in other United States geographies, particularly in the southwest. Next, we need to understand why the racial disparities exist and identify approaches that can be implemented to improve genetic testing across the United States for women with breast and ovarian cancers.

Dr. Arun conducts research characterizing risk factors in high-risk women with or without hereditary breast cancer mutations and assessing breast cancer biology in patients with breast cancer who have mutations of the BRCA1 or BRCA2 gene. She also runs clinical treatment trials in patients with BRCA mutations using PARP inhibitors.

FINANCIAL DISCLOSURE: Dr. Arun has received research funding from Invitae.

Dr. Arun is Professor in the Department of Breast Medical Oncology, Division of Cancer Medicine, and Co-Medical Director, Clinical Cancer Genetics Program, University of Texas MD Anderson Cancer Center, Houston, Texas.

References:

1. Kurian AW, Ward KC, Howlader N, et al. Genetic testing and results in a population-based cohort of breast cancer patients and ovarian cancer patients. J Clin Oncol. 2019;37:1305-1315.

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Mutations and the Importance of Genetic Testing - Cancer Network

Clinical exome sequencing has revolutionized genetic testing for children with inherited disorders, and Baylor College of Medicine researchers have led efforts to apply these DNA methods in the clinic. Nevertheless, in more than two-thirds of cases, the underlying genetic changes in children who undergo sequencing are unknown. Researchers everywhere are looking to new methods to analyze exome sequencing data to look for new associations between specific genes and those rare genetic diseases called Mendelian disorders. Investigators at theHuman Genome Sequencing Centerhave developed new approaches for large-scale analysis of Mendelian disorders, published today in theAmerican Journal of Human Genetics.

The investigators used an Apache Hadoop data lake, a data management platform, to aggregate the exome sequencing data from approximately 19,000 individuals from different sources. Using information from previously solved disease cases, they established methods to rapidly select candidates for Mendelian disease. They found 154 candidate disease-associating genes, which previously had no known association between mutation and rare genetic disease, according toAdam Hansen, lead author of the study and graduate student inmolecular and human geneticsat Baylor.

We found at least five people for each of these 154 genes that have very rare genetic mutations that we suspect might be causing disease, Hansen said. This shows the power of big data approaches toward accelerating the rate of discovery of associations between genes and rare diseases.

These computational methods solve the dual problems of large-scale data management and careful management of data access permission. saidDr. Richard Gibbs, study author and professor of molecular and human genetics and director of the Human Genome Sequencing Center at Baylor. They are perfect for outward display of data from the Baylor College of Medicine programs.

Exome sequencing currently only diagnoses 30 to 40% of patients, Hansen said. He hopes that diagnosis rate will increase with the discovery of new associations between mutations in certain genes and rare diseases.

The genetics community can now focus on genetic mutations in these genes when they see undiagnosed patients, Hansen said. Since our initial analysis, 19 of these genes have already been confirmed as disease-associating by independent researchers. The collective effort of the genetics community will advance our understanding of these genes and provide further evidence for their potential role in disease.

Other researchers at the Human Genome Sequencing Center who were involved in the study included Mullai Muragan, Donna Muzny, Fritz Sedlazeck, Aniko Sabo, Shalini Jhangiani, Kim Andrews, Michael Khayat, and Liwen Wang.

This work was supported in part by grants UM1 HG008898 from the National Human Genome Research Institute (NHBLI) to the Baylor College of Medicine Center for Common Disease Genetics; UM1 HG006542 from the NHGRI/National Heart, Lung, and Blood Institute (NHLBI) to the Baylor Hopkins Center for Mendelian Genomics; R01 NS058529 and R35 NS105078 (J.R.L.) from the National Institute of Neurological Disorders and Stroke (NINDS); and P50 DK096415 (N.K.) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

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Connecting gene mutations, rare genetic diseases - Baylor College of Medicine News