EDITORIAL J Oral Maxillofac Surg 73:795-796, 2015
Precision Medicine—Implications for Oral-Maxillofacial Surgery recognized, it was still usually difficult to predict whether the disease would clinically manifest in progeny. Furthermore, even if it was clear that a disease or deformity would pass to offspring, short of recommending they not bear children or use a surrogate parent, physicians had nothing to offer prospective parents. However, the growing understanding of and ability to possibly manipulate defective genes could bring the possibility of allowing those with the abnormal genes to still bear normal children. The implications of precision medicine for oralmaxillofacial (OM) surgery exist on two levels: 1) in our role as surgeon healers, and 2) to those in our specialty who are surgeon researchers. There are also implications to each of us having individual and family health concerns. Precision medicine will have a great effect on how we think about our patients in our daily clinical practice. The costs in time and money to perform DNA sequencing are plummeting. What a little more than 10 years ago required many months and $100 million to sequence one genome can now be done within a couple of days for less than $10,000. Therefore, the day is quickly approaching when an OM surgeon will see patients who have had their DNA sequenced and are ‘‘eligible’’ for precision medicine. This will open the door to studies that will help guide our treatment plans. For example, it is known that 1 in 15,000 exposures to the drug amoxicillin-clavulanic acid results in severe liver injury. With precision medicine comes the promise that we will know why this occurs and be able to avoid giving that drug to susceptible patients. OM surgeons who practice surgical oncology will eventually be able to take advantage of the evolving ability to identify tumor markers in a person’s DNA. These markers will help show individual patient susceptibility to the malignancy and, as importantly, help guide clinicians to optimal prevention and treatment practices. Actress Angelina Jolie’s decision regarding breast and ovary removal is an example of the use of this strategy. When similar approaches are possible with malignancies affecting the orofacial region, we will also be able to give similar clinical guidance. Our growing availability to know individual genomic data also holds the promise of other ways OM surgeons might be able to practice precision medicine. Our understanding of the determinants of facial
The 2015 State of the Union contained a brief reference to the topic of precision medicine. President Obama was referring to the improving ability of caregivers to individualize the treatment of many diseases. Despite the brevity of the message, the development of precision medicine has monumental implications. An improved understanding of the genetic pathogenesis of disease will: 1) advance our ability to assess disease susceptibility and identify risk preventions, 2) provide a means to better classify and diagnose disease, 3) better target therapy using existing and novel, biologically based modalities, and 4) reduce treatment side effects and make patient monitoring more precise. The President’s budget request includes funding to help promote the development of precision medicine, but precision medicine already has large tailwinds at its back. This is due to the promise of improved disease and deformity treatment and prevention. The precision medicine concept has arisen out of the science of genomics, proteomics, and bioinformatics. The ability to determine the entire genetic sequences of individuals opens the door to the capability of recognizing differences in code that affect human health and form. This new understanding of diseases is revolutionary, permitting investigators to subdivide diseases such as certain malignancies that were previously lumped together based on factors such as patient signs and symptoms or similar histopathologic appearances. Each new division of disease could carry a different pathophysiology, set of biochemical markers, and response to various treatment strategies. Thus, patients might have previously all received the same treatment for their disease or perhaps a variety of different treatments. Some of those treatments seemed to work for some patients, but not for others, without any rhyme or reason. However, when subdivided by the relevant genetic differences, it will be possible to perform investigations that will reveal why patients previously thought to all have the identical problem differ in their response to various management strategies. The results of such research will open the door to the individualization of medical care. Genomics has also improved our ability to better understand the hereditary basis of disease and deformity. Although for many diseases, a genetic basis was well
795
796 deformities is still extremely limited. Although we perform corrective procedures on patients with deformities, consider the possibility of being able to limit or eliminate deformity development with genomic information. Precision medicine might give us the tools to help guide the normal development of the jaws and face. Consider those with Pierre Robin sequence. It is conceivable that instead of a series of major operations, the clinician will be able to use factors developed using genomic data to lessen the magnitude of the deformity, allowing for more straightforward and precise surgery. The development of factors to correct for the DNA deformity might be a part of prenatal care for women identified as having an affected fetus. A growing understanding of genomics could also allow us to better understand a variety of conditions such as patient susceptibility to temporomandibular joint disorders, the variability in response to pain relieving and anesthetic drugs, why certain patients develop medication-related osteonecrosis of the jaws, why some patients experience severe drug reactions or interactions, why mucosal diseases such as lichen planus, aphthous ulcers, or pemphigus occur in some individuals and not others, why those with basal cell nevus syndrome develop jaw keratocysts, and so forth. The implications are truly mind-boggling. A new taxonomy of maxillofacial-associated conditions will need to be developed as our understanding of disease pathophysiology grows through genomic data analysis. Our improved knowledge of the pathogenesis of disease and mechanisms controlling disease manifestations will guide both treatment and preventative strategies. Precision medicine will also involve clinicians modulating patient signs and symptoms. The potential of being able to practice precision medicine offers boundless opportunities to OM surgeon researchers. The field of genomics, particularly as it relates to diseases and deformities of the orofacial region, is in its early infancy. However, the decreasing costs of DNA sequencing make research in orofacial genomics both possible and affordable. Therefore, projects can be conceived and funding proposals developed to obtain genomic information from patients and, when relevant, from their family
EDITORIAL
members to begin to find the genetic determinants responsible for disease or deformity occurrence. The results of such research can then be used to individualize the care of patients. For more rare conditions, practice-based office networks, similar to those being formed by the American Association of Oral and Maxillofacial Surgeons, will be beneficial. OM surgeon researchers should seek to partner with those doing genomic research to establish projects that will help uncover the genetic basis of diseases and deformities affecting the orofacial region. Finally, the ability to fully sequence one’s genome has implications for each of us as individuals. The ability to better understand disease development, particularly for common conditions such as Alzheimer’s disease, cancer, and cardiovascular diseases, promises to improve the health of each of us, as well as our families and fellow humans. The day will come when even those of us with a known genetic predisposition to a disease or deformity can receive interventions that will lessen or eliminate the likelihood of the problem affecting us. Just as with many new vistas in our abilities to control human diseases and deformities, ethical issues arise. This is particularly true with genomic research and care, because new boundaries of patient privacy will need to be drawn. In addition, gene manipulation is a cause of concern by many for both moral and ethical reasons. Precision medicine brings the promise of improving our ability as clinicians to more precisely diagnose, manage, and even prevent human disease and deformities. This field also holds limitless opportunities for scientific investigations. It brings similar benefits to each of us as potential patients. We, as oral-maxillofacial surgeons, should recognize, appreciate, and reflect on the implications precision medicine brings. JAMES R. HUPP, DMD, MD, JD Editor-in-Chief
Ó 2015 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons http://dx.doi.org/10.1016/j.joms.2015.03.002
Precision Medicine—Implications for Oral-Maxillofacial Surgery recognized, it was still usually difficult to predict whether the disease would clinically manifest in progeny. Furthermore, even if it was clear that a disease or deformity would pass to offspring, short of recommending they not bear children or use a surrogate parent, physicians had nothing to offer prospective parents. However, the growing understanding of and ability to possibly manipulate defective genes could bring the possibility of allowing those with the abnormal genes to still bear normal children. The implications of precision medicine for oralmaxillofacial (OM) surgery exist on two levels: 1) in our role as surgeon healers, and 2) to those in our specialty who are surgeon researchers. There are also implications to each of us having individual and family health concerns. Precision medicine will have a great effect on how we think about our patients in our daily clinical practice. The costs in time and money to perform DNA sequencing are plummeting. What a little more than 10 years ago required many months and $100 million to sequence one genome can now be done within a couple of days for less than $10,000. Therefore, the day is quickly approaching when an OM surgeon will see patients who have had their DNA sequenced and are ‘‘eligible’’ for precision medicine. This will open the door to studies that will help guide our treatment plans. For example, it is known that 1 in 15,000 exposures to the drug amoxicillin-clavulanic acid results in severe liver injury. With precision medicine comes the promise that we will know why this occurs and be able to avoid giving that drug to susceptible patients. OM surgeons who practice surgical oncology will eventually be able to take advantage of the evolving ability to identify tumor markers in a person’s DNA. These markers will help show individual patient susceptibility to the malignancy and, as importantly, help guide clinicians to optimal prevention and treatment practices. Actress Angelina Jolie’s decision regarding breast and ovary removal is an example of the use of this strategy. When similar approaches are possible with malignancies affecting the orofacial region, we will also be able to give similar clinical guidance. Our growing availability to know individual genomic data also holds the promise of other ways OM surgeons might be able to practice precision medicine. Our understanding of the determinants of facial
The 2015 State of the Union contained a brief reference to the topic of precision medicine. President Obama was referring to the improving ability of caregivers to individualize the treatment of many diseases. Despite the brevity of the message, the development of precision medicine has monumental implications. An improved understanding of the genetic pathogenesis of disease will: 1) advance our ability to assess disease susceptibility and identify risk preventions, 2) provide a means to better classify and diagnose disease, 3) better target therapy using existing and novel, biologically based modalities, and 4) reduce treatment side effects and make patient monitoring more precise. The President’s budget request includes funding to help promote the development of precision medicine, but precision medicine already has large tailwinds at its back. This is due to the promise of improved disease and deformity treatment and prevention. The precision medicine concept has arisen out of the science of genomics, proteomics, and bioinformatics. The ability to determine the entire genetic sequences of individuals opens the door to the capability of recognizing differences in code that affect human health and form. This new understanding of diseases is revolutionary, permitting investigators to subdivide diseases such as certain malignancies that were previously lumped together based on factors such as patient signs and symptoms or similar histopathologic appearances. Each new division of disease could carry a different pathophysiology, set of biochemical markers, and response to various treatment strategies. Thus, patients might have previously all received the same treatment for their disease or perhaps a variety of different treatments. Some of those treatments seemed to work for some patients, but not for others, without any rhyme or reason. However, when subdivided by the relevant genetic differences, it will be possible to perform investigations that will reveal why patients previously thought to all have the identical problem differ in their response to various management strategies. The results of such research will open the door to the individualization of medical care. Genomics has also improved our ability to better understand the hereditary basis of disease and deformity. Although for many diseases, a genetic basis was well
795
796 deformities is still extremely limited. Although we perform corrective procedures on patients with deformities, consider the possibility of being able to limit or eliminate deformity development with genomic information. Precision medicine might give us the tools to help guide the normal development of the jaws and face. Consider those with Pierre Robin sequence. It is conceivable that instead of a series of major operations, the clinician will be able to use factors developed using genomic data to lessen the magnitude of the deformity, allowing for more straightforward and precise surgery. The development of factors to correct for the DNA deformity might be a part of prenatal care for women identified as having an affected fetus. A growing understanding of genomics could also allow us to better understand a variety of conditions such as patient susceptibility to temporomandibular joint disorders, the variability in response to pain relieving and anesthetic drugs, why certain patients develop medication-related osteonecrosis of the jaws, why some patients experience severe drug reactions or interactions, why mucosal diseases such as lichen planus, aphthous ulcers, or pemphigus occur in some individuals and not others, why those with basal cell nevus syndrome develop jaw keratocysts, and so forth. The implications are truly mind-boggling. A new taxonomy of maxillofacial-associated conditions will need to be developed as our understanding of disease pathophysiology grows through genomic data analysis. Our improved knowledge of the pathogenesis of disease and mechanisms controlling disease manifestations will guide both treatment and preventative strategies. Precision medicine will also involve clinicians modulating patient signs and symptoms. The potential of being able to practice precision medicine offers boundless opportunities to OM surgeon researchers. The field of genomics, particularly as it relates to diseases and deformities of the orofacial region, is in its early infancy. However, the decreasing costs of DNA sequencing make research in orofacial genomics both possible and affordable. Therefore, projects can be conceived and funding proposals developed to obtain genomic information from patients and, when relevant, from their family
EDITORIAL
members to begin to find the genetic determinants responsible for disease or deformity occurrence. The results of such research can then be used to individualize the care of patients. For more rare conditions, practice-based office networks, similar to those being formed by the American Association of Oral and Maxillofacial Surgeons, will be beneficial. OM surgeon researchers should seek to partner with those doing genomic research to establish projects that will help uncover the genetic basis of diseases and deformities affecting the orofacial region. Finally, the ability to fully sequence one’s genome has implications for each of us as individuals. The ability to better understand disease development, particularly for common conditions such as Alzheimer’s disease, cancer, and cardiovascular diseases, promises to improve the health of each of us, as well as our families and fellow humans. The day will come when even those of us with a known genetic predisposition to a disease or deformity can receive interventions that will lessen or eliminate the likelihood of the problem affecting us. Just as with many new vistas in our abilities to control human diseases and deformities, ethical issues arise. This is particularly true with genomic research and care, because new boundaries of patient privacy will need to be drawn. In addition, gene manipulation is a cause of concern by many for both moral and ethical reasons. Precision medicine brings the promise of improving our ability as clinicians to more precisely diagnose, manage, and even prevent human disease and deformities. This field also holds limitless opportunities for scientific investigations. It brings similar benefits to each of us as potential patients. We, as oral-maxillofacial surgeons, should recognize, appreciate, and reflect on the implications precision medicine brings. JAMES R. HUPP, DMD, MD, JD Editor-in-Chief
Ó 2015 Published by Elsevier Inc on behalf of the American Association of Oral and Maxillofacial Surgeons http://dx.doi.org/10.1016/j.joms.2015.03.002
