Breast cancer accounts for nearly 1 in 3 cancers diagnosed in U.S. women [2]. In October 2010, the National Breast Cancer Coalition (NBCC) called for a vaccine for breast cancer with a deadline of 2020. Almost a year later, GE’s healthymagination initiative has also focused on breast cancer with a target of 2020.

Modeled after GE’s ecomagination challenge, which resulted in over 5,000 submitted ideas and $134 million in investments and partnerships by GE, the new healthymagination challenge focuses on improving early detection of breast cancer at the molecular level. GE’s first healthymagination Challenge is an open call to action for oncology researchers, businesses, students, and healthcare innovators. Through the Challenge, GE and its venture capital partners will award up to $100 million to fund the best ideas to improve breast cancer diagnostics. The are several goals to the Challenge:

1. Improve early breast cancer detection and allow for more accurate diagnosis
2. Better understand tumors associated with triple negative breast cancer, which is less responsive to standard treatments and is typically more aggressive
3. Better understand the molecular similarities between breast cancer and other solid tumors

Jeff Immelt, CEO and Chairman, GE, said [3]:

We envision a day when cancer is no longer a deadly disease. When you add our cutting edge cancer detection technologies to the innovative ideas of our new partners, it’s a powerful formula for tackling cancer and helping doctors and researchers improve care.

In partnership with O’Reilly Media, the effort will also feature a special focus on data (CEO and founder, Tim O’Reilly, is an advocate for using data science to spur innovation). A series of code-a-thons or “data challenges” will be held to engage the data science community in finding new applications for breast cancer data.

To enable analysis and further accelerate innovation, GE is also investing in the development of a first-in-kind “super database” that will consolidate clinical, pathology, therapy and outcomes data. The database will be available in collaboration with leading cancer research organizations, as well as NGO and government groups, starting with relevant cancer data from GE’s Medical Quality Improvement Consortium (MQIC); Clarient, a cancer diagnostics and GE Healthcare Company; The Premier healthcare alliance; and the U.S. Department of Health & Human Services.

In addition, Immelt also said that GE will invest $1 billion over the next five years on research and development programs to expand its suite of advanced technologies and solutions for cancer detection and treatment. At the September event, GE presented several new technologies:

1. GE SenoCase, a new concept in mobile mammography that will deliver breast cancer screening capabilities to millions of women around the world who lack access to existing screening options
2. GE PET Tracer, a new Positron Emission Tomography (PET) tracer technology in development that will inform doctors if cancer treatments are working, very early in the course of treatment, by measuring new blood vessel formation in tumors
3. GE SenoBright Contrast Enhanced Spectral Mammography (CESM), a technique that helps radiologists localize a known or suspected breast cancer lesion

Lastly, GE announced a three-year partnership with Susan. G Komen for the Cure to forge first-in-kind programs that bring the latest breast cancer technologies to more women in the United States and around the world. Initially, these programs will run in Wyoming (one of the most rural states in the U.S.), Saudi Arabia and China.

GE will publicly track progress against this cancer initiative at healthymagination.com.

References

1. GE Launches New Commitment to Accelerate Cancer Fight: Integrated Tech Portfolio and Collaboration with Doctors and Researchers to Deliver Better Care to 10M Patients by 2020. GE reports. 2011 Sep 15.
2. Breast Cancer Facts & Figures 2011-2012. American Cancer Society. Accessed 2011 Nov 17.
3. GE and Partners Aim to Speed Fight Against Cancer, Starting with Breast Cancer. Healthymagniation press release. 2011 Sep 15.

Sickle cell disease is a recessive genetic disorder caused by a single base mutation in the gene for hemoglobin, beta locus (HBB). Hemoglobin is responsible for transporting oxygen throughout the body. People living with sickle cell disease have two copies of an altered gene that produces sickle hemoglobin instead of normal adult hemoglobin. Sickle hemoglobin changes shape after releasing its oxygen, causing the red blood cell to become stiff, misshapen and sticky, and slowing blood flow to tissues. This process damages organs and causes pain.

Susan B. Shurin, M.D., acting director of the NIH’s National Heart, Lung, and Blood Institute, which co-funded the study, said:

This discovery provides an important new target for future therapies in people with sickle cell disease. More work is needed before it will be possible to test such therapies in people, but this study demonstrates that the approach works in principle.

Researchers at Harvard Medical School in Boston and the University of Texas at Austin corrected sickle cell disease in mice that had been bred to have the inherited blood disorder. The National Heart, Lung, and Blood Institute, the National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) — all part of the NIH — funded the research. The results of the study were recently published in the online edition of the journal Science [1].

The study tested a new approach to increasing the production of a third form of hemoglobin — fetal hemoglobin. Production of fetal hemoglobin predominates before birth, but turns off thereafter as adult hemoglobin production takes over. People with sickle cell disease are unable to make normal adult hemoglobin, and instead make sickle hemoglobin starting in infancy.

An elevated level of fetal hemoglobin within the red blood cell reduces the tendency of sickle hemoglobin to change the shape of red blood cells. Considerable NIH- supported research has shown that the drug hydroxyurea increases production of fetal hemoglobin and reduces the number of pain crises and other complications of sickle cell disease in adults and children. However, not all patients respond well to hydroxyurea, and adverse side effects are a concern.

The current study explores a more targeted approach to increasing fetal hemoglobin production. It builds upon earlier studies by Stuart Orkin, M.D., and his team at Harvard Medical School, Children’s Hospital of Boston, and the Howard Hughes Medical Institute, Boston, which discovered that a protein called B-cel CLL/Lymphoma 11A (BCL11A) normally suppresses the production of fetal hemoglobin soon after birth [2]. The researchers viewed the BCL11A protein as a target for therapy and decided to see what would happen if they blocked production of the protein.

Griffin P. Rodgers, M.D., M.A.C.P., director of NIDDK, said:

This important advance in the battle against sickle cell disease is another outstanding example of how great things can happen when work proceeds from bench to bedside, and back to the bench. We hope that one day, this discovery and any that build upon it will translate into a viable treatment option for those suffering from this devastating illness.

The current paper details how the research team silenced the mouse gene that produces the BCL11A protein in mice with sickle cell disease. Silencing the gene turned off production of the BCL11A protein and allowed the adult mice to continue to produce fetal hemoglobin. It appears to have eliminated disease symptoms without affecting other aspects of blood production.

Approximately 100,000 Americans live with sickle cell disease. It is most prevalent in people of African, Hispanic, Mediterranean, and Middle Eastern descent. There is no widely available cure for sickle cell disease. Bone marrow transplants have cured some patients, but the treatment is not without risk and most patients do not have relatives who can donate compatible and healthy bone marrow to them.

Source: NIH News

References

1. Xu et al. Correction of Sickle Cell Disease in Adult Mice by Interference with Fetal Hemoglobin Silencing. Science. 2011 Oct 13. [Epub ahead of print]
   View abstract
2. Sankaran et al. Human fetal hemoglobin expression is regulated by the developmental stage-specific repressor BCL11A. Science. 2008 Dec 19;322(5909):1839-42.
   View abstract

Asthma is a chronic inflammatory disease that affects 24 million people in the United States and roughly 300 million people worldwide [2]. The disease affects the lungs, causing repeated episodes of wheezing, breathlessness, chest tightness, and nighttime or early morning coughing. A number of factors can influence how severely the disease affects people and how well they respond to treatments. In addition to avoiding the triggers that can cause an attack, asthma can also be controlled by taking medication. However, the response to treatment is characterized by high interindividual variability. Poor response to inhaled corticosteroids often runs in families, suggesting that genetics plays a role in how people respond to the treatment.

To identify a gene variant, researchers from Brigham and Women’s Hospital and Harvard Medical School analyzed the genetic information from over 1,000 people enrolled in five separate clinical trials evaluating different steroid treatments for asthma. Investigators first conducted a genome-wide scan of the DNA of children and their parents enrolled in the Childhood Asthma Management Program, a multicenter, randomized, double-masked clinical trial designed to determine the long-term effects of three inhaled treatments for mild to moderate childhood asthma: budesonide (a glucocorticoid used daily) and albuterol (a short-acting beta-agonist bronchodilator used as needed); nedocromil (a nonsteroid anti-inflammatory agent used daily) and albuterol; and placebo and albuterol [3]. The scan identified 13 single nucleotide polymorphisms (SNPs) encompassing eight genes, including a variant in a gene called glucocorticoid induced transcript 1 (GLCCI1), which appeared to be associated with poor response to inhaled corticosteroids.

Researchers then verified the association in three additional studies on people with asthma, both children and adults. Due to the small numbers of subjects in other racial groups, the analyses were restricted to white participants.

The scientists found that people carrying two copies of the GLCCI1 variant were more than twice as likely to respond poorly to inhaled corticosteroid treatment as individuals with two copies of the normal GLCCI1 gene. Those who responded poorly had an average of one-third the level of lung improvement following inhaler treatment as did people with two normal copies of the gene.

Approximately 1-in-6 study participants had two copies of the GLCCI1 variant, which is thought to work together with other genetic and environmental factors to affect response to inhaled corticosteroids. Additional studies are needed to understand how GLCCI1 functions in the lungs and to explore whether it contributes to therapeutic response in patients of other ethnic groups.

Dr. Jeffrey Drazen, NEJM Editor-in-Chief, said in an editorial that the study brings researchers closer to being able to identify which patients are most likely to respond to treatment from inhaled steroids but that clinical trials are necessary to determine whether knowledge of this information leads to better clinical outcomes [4].

Susan Shurin, M.D., acting director of the National Heart, Lung, and Blood Institute (NHLBI), a component of the National Institutes of Health (NIH) that plans, conducts, and supports research related to the causes, prevention, diagnosis and treatment of heart, blood vessel, lung, and blood diseases, said [5]:

This finding helps to explain the genetic basis for the long-standing observation that some people do not respond well to what is a common asthma treatment. The study illustrates the importance of research examining the relationship between genetic makeup and response to therapy for asthma, and underscores the need for personalized treatment for those who have it.

Asthma affects people of all ages, but it most often starts during childhood. In the United States, more than 24 million people have asthma; 7 million of these people are children [2]. For more information on asthma — what it is, its effects and how it is diagnosed and treated — check out the CDC’s You Can Control Your Asthma brochure.

References

1. Tantisira et al. Genomewide Association between GLCCI1 and Response to Glucocorticoid Therapy in Asthma. Epub 2011 Sept 26.
2. FASTSTATS — Asthma. Centers for Disease Control and Prevention. Accessed 2011 Sep 26.
3. The Childhood Asthma Management Program (CAMP): design, rationale, and methods. Childhood Asthma Management Program Research Group. Control Clin Trials. 1999 Feb;20(1):91-120.
   View abstract
4. Drazen, JM. A Step toward Personalized Asthma Treatment. Epub 2011 Sept 26.
5. NIH-funded study connects gene variant to response to asthma drugs. NIH News press release. 2011 Sep 26.

A team led by Atul J. Butte, M.D., Ph.D. at Stanford University used data from the National Institutes of Health National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), a publicly available database that contains the results of thousands of genomic studies submitted by researchers around the world on a wide range of topics. The GEO database catalogs changes in gene expression under various conditions, such as in diseased tissues or in response to medications.

Butte’s group focused on 100 diseases and 164 drugs. They created a computer algorithm that searched for and matched studies where a drug created a change in gene expression that was opposite to the gene expression caused by a disease. Many of the drug-disease matches were known and are already in clinical use, supporting the validity of the approach. For example, the algorithm correctly predicted that prednisolone could treat Crohn’s disease, a condition for which it is a standard therapy.

Other matches were surprising. In particular, the algorithm matched an anti-ulcer drug (cimetidine) with lung cancer, and an anticonvulsant drug used in epilepsy (topiramate) with inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis.

The researchers then tested the two drugs — both generics — in animal models. Cimetidine slowed the growth of cancer cells in a mouse model of lung cancer compared to mice that did not receive the drug. Topiramate decreased the symptoms of bowel disease — diarrhea, inflammation, ulcers and microscopic damage in the colon — in rats, sometimes even better than prednisolone.

Further studies are needed to validate the clinical potential of cimetidine as a therapy for lung cancer and topiramate as a therapy for inflammatory bowel disease. Nevertheless, the studies provide proof-of-principle that the matching of drug-disease gene expression profiles are useful to repurpose drugs.

Yves A. Lussier, M.D., an Associate Professor of medicine and engineering at the University of Illinois at Chicago who co-authored a commentary on the research in Science Translational Medicine, wrote [3]:

This emergent genome-wide property of directionality [between genome-wide mRNA expression and a clinical phenotype] may ultimately translate into medical practice as a clinical finding analogous to an arrhythmia seen on electrocardiogram. Arguably, physicians could incorporate these clinicogenomic findings in their practice to improve the process of treatment decision-making.

Pharmaceutical companies have increasingly turned to drug repurposing as a means of drug discovery. A significant advantage of drug repurposing is that the repurposed drug has already passed a significant number of toxicity tests and has an established safety profile, so it can move through development at an accelerated pace.

Butte is also co-founder of NuMedii, an early stage therapeutics company focused on finding new clinical applications for existing drugs; he is also chairman of the company’s scientific advisory board. The two published studies should serve to validate the company’s computational method and will likely attract pharmaceutical companies that are eager to find new uses for drugs in their pipeline.

References

1. Sirota et al. Discovery and Preclinical Validation of Drug Indications Using Compendia of Public Gene Expression Data. Sci Transl Med. 2011 Aug 17.
   View abstract
2. Dudley et al. Computational Repositioning of the Anticonvulsant Topiramate for Inflammatory Bowel Disease. Sci Transl Med. 2011 Aug 17.
   View abstract
3. Lussier and Chen. The Emergence of Genome-Based Drug Repositioning. Sci Transl Med. 2011 Aug 17.
   View abstract

NBC Nightly News aired an intriguing story last night about dogs who have the ability to detect ovarian cancer [1]. The story referenced a new study published in the European Respiratory Journal that focused on canine scent detection for the diagnosis of lung cancer [2].

The outcome of a patient with lung cancer, like many other cancers, depends in large part on early diagnosis. Exhaled breath of patients may represent the ideal lab specimen for cancer screening. However, current diagnostic sensor technologies are unable to identify a clear target. German scientists used four sniffer dogs to test the strength of the presence of an as-of-yet unknown compound in the breath of patients with lung cancer.

That as-of-yet unknown compound is a biomarker — a protein or set of proteins specific to lung cancer that, by nature of the tumor being in a patient’s lungs, is exhaled.

In the study, researchers had patients with blow into test tubes filled with a fleece material that absorbs compounds suspended in the breath. Following a rigid scientific protocol, sniffer dogs were presented with exhalation samples from either 110 healthy individuals, 60 patients with confirmed lung cancer or 50 patients with chronic obstructive pulmonary disease (COPD). The dogs were trained to lie down next to test tubes that came from patients with lung cancer. Scientists analyzed patient history, drug administration and clinicopathological data to identify potential bias or confounders.

The results are impressive. Lung cancer was identified by the four dogs with an overall sensitivity of 71% and a specificity of 93%.

The detection of lung cancer was independent of the patient having COPD as well as the presence of tobacco smoke and food odors.

Although two drugs were identified as potential cofounders — meaning the dogs may have been detecting drugs used to treat lung cancer rather than the cancer itself — the results are still intriguing. Researchers are working on a follow-up study to determine if the dogs react to other types of cancer [3].

Check out a video of the NBC News story below:

References

1. Trained dogs can help detect cancer. NBC Nightly News. 2011 Aug 18.
2. Ehmann et al. Canine scent detection in the diagnosis of lung cancer: Revisiting a puzzling phenomenon. Eur Respir J 2011. Published ahead of print.
3. Fine dog noses sniff out lung cancer. Robert-Bosch-Krankenhaus. 2011 Aug 18.

The cytochrome P450 enzyme superfamily (abbreviated as CYP) are the major enzymes involved in drug metabolism and bioactivation. Cytochrome P450, subfamily IIIA, polypeptide 4 (CYP3A4) is the primary CYP expressed in adult human liver. It is both continuously expressed as well as activated by a variety of clinically used drugs. CYP3A4 activity is known to show a significant variability not only between different people but also within the same person at different times. The reason for this variability is unknown.

The goal of the present study was to test the hypothesis that plasma concentrations of three immunosuppressant drugs — tacrolimus, sirolimus and cyclosporine — show seasonal variations associated with increased CYP34A4 enzyme via vitamin D. These drugs were used because they are dependent on the CYP3A4 metabolic pathway and most patients taking these drugs use them for long periods of time and require repeated concentration determinations.

The researchers reviewed almost 70,000 analyses from patients who had undergone regular monitoring of the levels of drugs in their blood. They found that samples collected during the summer (July-September) had significantly lower dose-corrected concentrations of tacrolimus and sirolimus compared to those collected during the winter (January – March). In contrast, no change was detected in cyclosporine concentrations.

A more detailed analysis found that the concentrations of tacrolimus and sirolimus vary throughout the year, closely reflecting the changes in the level of vitamin D in the body. The body depends on sunlight to form vitamin D. The highest levels of vitamin D in patients taking part in the study were reached when the levels of the drugs were lowest.

Although the results are correlative, not causal, scientists think the connection between sunlight, vitamin D and the bioavailability of sirolimus and tacrolimus arises from the activation by vitamin D of the liver detoxification system, specifically by increasing the amount CYP3A4. In turn, CYP3A4 is responsible for the breakdown of tacrolimus and sirolimus.

Jonatan Lindh at the Karolinska Institutet Department of Laboratory Medicine and lead author of the study said [2]:

If the breakdown capacity increases, then higher doses of a drug are normally required in order to achieve the same effect. More research will be needed to confirm the results, but CYP3A4 is considered to be the most important enzyme in drug turnover in the body, and the results may have significance for many drugs.

Just three years ago, we reported on the International Serious Adverse Events Consortium (SAEC), which announced plans to identify genetic markers that predicted drug-related serious adverse events. The results of the current study suggest that individual differences in the effects of drugs is even more intricate than just genetics alone.

References

1. Lindh et al. Seasonal variation in blood drug concentrations and a potential relationship to vitamin d. Drug Metab Dispos. 2011 May;39(5):933-7. Epub 2011 Feb 24.
   View abstract
2. Sunlight can influence the breakdown of medicines in the body. Karolinska Institutet. 2011 Mar 9.

Interestingly, the strategic plan really isn’t a strategic plan but a list of issues to be addressed. And on this note, Daniel MacArthur, a genomics researcher and author of Wired’s Genetic Future, found the NHGRI document frustrating to read [2]:

… this is an impressive, worthwhile and highly readable piece of work, but one that ultimately feels unfinished. As research dollars begin to get tighter, there is an urgent need for an actual strategic plan for building the resources and tools required to make genomic medicine a reality within a realistic budget.

In other words: a specific NHGRI funding plan to overcome the issues. This could prove difficult in the current U.S. fiscal environment. Even though President Obama has resisted cuts to biomedical research funding in his 2012 budget proposal, the outlook isn’t bright. Decreasing NIH funding for short-range budget goals will disrupt five-year-long longitudinal studies make it impossible to start new research [3]. Moreover, it will hurt U.S. standing as the world leader in biomedical advances.

Five research domains of the NHGR plan

The NHGRI vision is framed in terms of five research domains. They span activities from basic research to how the human genome is organized and functions to clinical applications that will use knowledge of the genome and genomic technologies to improve medical care and health maintenance. The research domains are:

1. Understanding the structure of genomes
2. Understanding the biology of genomes
3. Understanding the biology of disease
4. Advancing the science of medicine
5. Improving the effectiveness of healthcare

The plan also emphasizes three additional areas of interest that are important across those five domains: informatics, education and societal implications.

Because the NHGRI’s strategic plan moves forward on multiple fronts, the anticipate it to have several audiences. It obviously speaks to genomic researchers. But as genomics is permeating many areas of society, as well as science, it also offers opportunities for students of law, ethics, sociology and public policy as well as students in basic science, clinical science and clinical medicine.

Watch NHGRI Director Eric Green talk about the strategic plan and the research domains outlined in the strategy:

References

1. Green, Guyer & NHGRI. Charting a course for genomic medicine from base pairs to bedside. Nature 470, 204–213.
2. When Is A Strategic Plan Not A Strategic Plan? Genetic Future, Wired. 2011 Feb 15.
3. Budget cuts at the NIH: Department of nose-cutting, face-spiting. The Economist. 2011 Mar 9.

In December 2010, VBI researchers discovered a four-nucleotide repeat (AAAG) in the estrogen-related receptor gamma (ESRRG) gene, which indicates an individual’s genetic susceptibility to breast cancer [2]. Longer DNA sequences of the repetitive microsatellite were much more likely to be present in breast cancer patients than healthy volunteers; patients with a greater number of copies of the repeat in the promoter region of the ESRRG gene have a 3-fold higher cancer susceptibility rate than those who do not.

In the present study, instead of focusing on a single gene, the scientists created a design for a new DNA microarray that allowed them to measure the over 2 million microsatellites in the human genome in a single experiment. They evaluated the global microsatellite content in the genomes of 72 cancer, cancer-free, and high risk patient and cell line samples.

A unique, reproducible and statistically significant motif of 18 pattern-specific microsatellite families was identified in germline and tumor DNA from breast cancer patients but not in germline DNA of cancer-free patients or in breast cancer patients with BRCA1 or BRCA2 mutations.

These 18 pattern-specific microsatellite families suggest a new mechanism disrupting the genome in cancer patients and may represent a new breast cancer risk biomarker.

The repetitive motifs were also more pronounced in the germlines and tumors of colon cancer tumor patients (3/6 samples) and microsatellite unstable colon cancer cell lines. Although there were only 9 colon cancer samples, it suggests a more general role for microsatellites in the genome. The pattern on the microarray serves as the biomarker that can measure the amount of risk an individual has for developing cancer in the future.

Harold “Skip” Garner, VBI executive director who leads the institute’s Medical Informatics and Systems Division, explained:

We have now arrived at a new biomarker — an indicator that could be used to evaluate the amount of risk that you have for developing cancer in the future. This is part of an effort to understand their (microsatellite) role in the genome and then proceed on directly towards something that is of utility in the clinic. What just came out in our paper is a description of the technology that allows us to very quickly and efficiently and inexpensively measure these two million places using a uniquely designed microarray … It’s the pattern on that microarray that provides us the information we need.

You can watch an interview with Dr. Garner discussing the research and its future implications below:

References

1. Galindo et al. Sporadic breast cancer patients’ germline DNA exhibit an AT-rich microsatellite signature. Genes Chromosomes Cancer. 2011 Apr;50(4):275-83. doi: 10.1002/gcc.20853. Epub 2011 Jan 14.
   View abstract
2. Genetic Biomarker for Risk of Breast Cancer Identified in “Junk” DNA. Biomarker Commons. 2010 Dec 20.

Initial funding of $11.25 million for the institute will be provided by the IU School of Medicine, the school’s Department of Medicine, Indiana University-Purdue University Indianapolis, the Indiana Physician Scientist Initiative and the Indiana University Melvin and Bren Simon Cancer Center. The institue’s members will be drawn from the IU schools of medicine, informatics and nursing.

Dr. David Flockhart, Director of the institute, said [1]:

Much of the future of health care is in personalized medicine, meaning more precise targeting of the right medication to the right patient at the right time. We believe it should lead to cost benefits — it clearly will be better for patients.

The mission of the Indiana Institute for Personalized Medicine will be to conduct research, train new specialists in personalized medicine and promote the translation of scientific discoveries into new more precise therapeutics for patient care. To help move scientific discoveries to patient bedsides, the institute will have a panel of IU scientists that will assist researchers moving their research beyond the laboratory stages. Initially, the advisory panel will have 21 members and be chaired by Wade Clapp, M.D., chairman of the Department of Pediatrics.

Mathew Palakal, Ph.D., associate dean for graduate studies and research at the School of Informatics said [1]:

Research in personalized medicine spans a broad spectrum from systems biology to nanomedicine to gene therapy. Our research in such areas as systems biology, biological network analysis and proteomics, along with our graduate programs in health informatics and bioinformatics, will enable informatics and the School of Informatics to play a significant role in the success of the institute.

Personalized Medicine and Systems Biology

Institute members will include staff from the IU school of Informatics, some of which may also be affiliated with the Indiana Center for Systems Biology and Personalized Medicine (CSBPM). Founded in 2008, the CSBPM works to bring new discoveries in biology to clinical applications. The center’s mission is to cultivate “systems biology” approaches to address translational biomedical research problems.

Researchers who examine complex biological systems often feel frustrated because they are unable to put all their data together, in many cases tens of thousands of individual measurements. CSBPM co-director Sunil S. Badve, director of the translational genomics core at the IU School of Medicine and a primary pathologist for breast cancer research, understands the frustrations of both clinicians and basic science researchers. In a 2009 story about the CSBPM, Badve said [3]:

Until recently, cancer was cancer. Technology has advanced, and now we look at hundreds of markers, thousands of markers, at a time. We know the whole genome. So the question is, are there differences in tumor A versus tumor B when it is the same kind of cancer? And, can we exploit those differences for therapy purposes? Is type A cancer more responsive to a certain type of chemotherapy? That is the basis of personalized medicine. Each person has an unusual tumor regardless of whether it is breast or colon or lung cancer, and each unusual tumor needs to be treated according to the characteristics of that tumor.

Personalized Medicine is Promoting Collaboration

A recent first-of-its-kind study from the Tufts Center for the Study of Drug Development to measure the pharma/biotech industry’s progress in developing personalized medicines found that it is “occupying a growing role in the clinical pipelines of drug developers, and is leading companies to change their R&D paradigms, including how they make go/no-go decisions” [4]. One of the most important findings from the Tufts study revealed that drug developers are teaming with external partners, including academic medical centers and diagnostics developers, to advance the science of personalized medicine. This demonstrates that the process of achieving personalized medicine is dependent on industry-academia and industry-physician collaboration and relationships.

References

1. IU Personalized Medicine Institute to Develop Targeted and Individualized Treatments. Indiana University School of Medicine News. 2011 Feb 8.
2. The New Science of Personalized Medicine: Translating the Promise into Practice. PricewaterhouseCoopers LLP. 2009 Oct.
3. Reassembling the Elephant. Research & Creative Activity. Indiana University Office of the Vice Provost for Research. Volume XXXI Number 2. 2009 Spring.
4. Personalized Medicines Are Shaping the Way R&D Is Done, According to Tufts Center for the Study of Drug Development. Tufts Center for the Study of Drug Development. 2010 Nov 16.

Molecular pathways that are implicated in single-gene disorders may hold important clues for the diagnosis and treatment of common disease, according to the strategic plan, Charting a Course for Genomic Medicine from Base Pairs to Bedside, in the Feb. 10 issue of the journal Nature [1]. The new strategic plan comes on the 10th anniversary of the first analysis of the human genome sequence. Eric Green, M.D., Ph.D., NHGRI director, said:

Researchers around the world are working towards a future when healthcare providers will use information about our individual genomes to better diagnose and treat disease. While significant challenges remain to our understanding of how the genome operates in health and disease, there are enough examples to say with confidence that genomics research will lead to important advances in medicine.

The new vision, produced in consultation with the research community over the past two and a half years, is framed in terms of five research domains. They span activities from basic research into how the human genome is organized and functions to clinical applications that will use knowledge of the genome and genomic technologies to improve medical care and health maintenance. The research domains are:

1. Understanding the structure of genomes
2. Understanding the biology of genomes
3. Understanding the biology of disease
4. Advancing the science of medicine
5. Improving the effectiveness of healthcare

The plan envisions continuing to expand the understanding of the biology of the genome, including creating more diverse and complete catalogs of genomic and other “-omic” information, along with new tools and technologies to develop and interrogate those catalogs. Investigators in all fields of biomedical research use these resources to identify the functional contributors within the genome that determine normal, healthy biology, as well as those that, when altered, lead to common as well as rare diseases.

The new sequencing technologies, which have been widely adopted in the past three years, are a major driver of the developments in genomics research. Co-author Mark Guyer, Ph.D., director of the NHGRI Division of Extramural Research, said:

It took all the sequencing capacity in the world about 13 years to produce the first human genome sequence. In 2003, around the time we completed the Human Genome Project, technology had improved to the point where 100 machines could sequence a human-sized genome in about three months. In 2011, one machine can produce a human-sized sequence in about five days.

DNA sequencing technologies, however, are just one of the tools needed to answer the research questions that will advance human health. Technological improvements in many other areas will be critical to successfully integrate genomic knowledge into clinical care. The plan calls for fast, low-cost and highly accurate tools that will allow researchers to read and interpret much longer sections of the human genome and clinicians to use sequence information at the point of care.

The plan also calls for new technologies to measure the interaction between the environment, behavior and genes and for routine clinical applications of genomic tools such as newborn genetic screening and other types of diagnostic screening. It also calls for electronic medical records systems that integrate family histories and genomic data to generate personalized diagnoses, treatments, and prevention plans.

Development of new analytical methods, software tools and a robust computational infrastructure will be essential. Researchers need these tools for accessing, analyzing, integrating and storing the mountains of complex genomic data that will be gathered from thousands of individuals, according to the report.

With this ever-expanding body of knowledge, scientists will likely identify the genetic basis of most single-gene disorders in the next decade, the plan asserts. Furthermore, molecular pathways that are implicated in single-gene disorders may hold important clues for the diagnosis and treatment of common disease, the plan says.

The plan anticipates the increasingly important role of multi-disciplinary and international teams for collaboratively producing and analyzing comprehensive sets of data about a condition. Rapid data release for immediate research applications, which has been essential to genomic research, will continue to be fundamental for the field’s success, according to the plan.

Beyond technology, educational efforts will be critical to making genomic medicine practical for both clinicians and the public, according to the plan. Healthcare providers must be trained to interpret genomic information and to use it in counseling patients. Health consumers will need to familiarize themselves with genomic medicine so they can understand their personal risks, participate in clinical decisions, make the best use of new therapeutics and, if they so choose, modify their behaviors in response to genome-based health information. Legislators and policymakers must craft policies that continue to promote the confidentiality of participation in genomics research. Other policies will be needed to protect individual privacy and access to health coverage, and to encourage investment in genomic health technologies through intellectual property incentives.

Genomic medicine will only reach its full potential when its benefits become accessible to all, including at-risk and low-income individuals around the world. Towards this end, the plan notes the need for greater reliance on non-geneticist healthcare providers and a consideration of the larger societal implications of increasing genomic knowledge.

Dr. Green said:

Our base-pairs-to-bedside plan maps the next steps in the herculean endeavor not only to discover medical secrets hidden within the human genomes, but to bring those discoveries to the practitioner and patient. All of us in this field share a sense of urgency about using genomics for clinical applications. The challenges are enormous, but we believe that, working together, the goal of improving human health is within reach.

Dr. Green observed that genomic approaches already inform some medical treatments. Breast cancer and colorectal cancer patients are now tested for Her2 and KRAS gene mutations, respectively, in order to guide drug choices. Likewise, genetically guided prescriptions of the anti-retroviral abacavir (Ziagen) are now the standard of care for patients with HIV, and the uses of tamoxifen, clopidogrel (Plavix) and possibly warfarin will soon benefit from genetic guidance. These successes demonstrate that genomic science is already having an impact on medical care, and portend much wider application as genomics increasingly becomes an integral part of health research and development, Dr. Green said.

NHGRI is one of the 27 institutes and centers at the National Institutes of Health, an agency of the Department of Health and Human Services. Additional information about NHGRI can be found at its website, www.genome.gov.

Source: NIH News

References

1. Green, Guyer & NHGRI. Charting a course for genomic medicine from base pairs to bedside. Nature 470, 204–213.