Cancer Stem Cells
-Sylvia White
New information regarding the way cancer stem cells acquire energy may lead to cancer treatments that do not harm healthy cells. Recently, the University of Colorado Cancer Center discovered that unlike mature cancer cells that switch from cellular respiration to glycolysis, cancer stem cells do not continuously require glucose for energy. Rather, they need to make a switch from metabolizing sugar to metabolizing amino acids. Craig Jordan, PhD, investigator at the University of Colorado Cancer Center, and his team have used this newfound information to successfully conduct clinical treatments with acute myeloid leukemia (AML) patients. Considering the leukemia stem cells eventually depend solely on the uptake of amino acids as their energy source, when AML patients received venetoclax—a drug that inhibits cells’ ability to utilize amino acids—the leukemia stem cells died. Since healthy cells do not rely on amino acid metabolism, the leukemia stem cells were killed without damaging any healthy cells—adding to the success of the clinical trials. While the studies are proving quite prosperous, limitations still exist: the drug was only successful in killing the leukemia stem cells when it was the AML patient’s first treatment. Otherwise, it appears they gained the ability to switch to a lipid metabolism, making them resistant to the venetoclax treatment and capable of presuming growth later. Nonetheless, Jordan remains confident that this is the beginning to a new form of leukemia treatment that may expand to treat other cancer types as well.
Is the F.D.A. Contributing to the Opioid Epidemic?
-James He
In the United States, there is a large opioid epidemic, as the extent of opioid abuse is rapidly increasing each year. An opioid is a class of drugs that contains chemicals that bind to receptors in the brain associated with pain, reward, and addiction. Some common opioids include heroin and fentanyl, which is a synthetic opioid, and usually abused due to their morphine-like effects in relieving pain as well as their addictive properties.
However, in light of this, the Food and Drug Administration recently approved Dsuvia, a tablet form of sufentanil that is ten times stronger than fentanyl, a common drug used in hospitals for pain relief that is already heavily abused to contribute to tens of thousands of overdose deaths in past years. The F.D.A. saw the potential of the drug in hospitals, surgical centers, and other supervised medical facilities that may suitable uses for the drug, and perhaps even for wounded soldiers in combat that need a strong therapy delivered very rapidly. And in order to keep it from accelerating the opioid epidemic that has plagued the United States, the drug will be kept within the confines of a supervised medical facility, away from retail pharmaceutical markets and in the privacy of an individual’s home. Additionally, the F.D.A. may require post-market research studies to assess whether the drug produces more benefit than harm and whether it is deemed necessary in a medical setting, considering its potency and its potential for abuse. The makers of the drug, AcelRx, will also keep close measures on its proper distribution and use after it is released on the market next year to ensure that it’s used safely and contributes to better medical operations.
Despite these precautions, there is widespread controversy regarding the approval of this drug. Even the F.D.A.’s advisory committee chairman, Dr. Raeford Brown, expressed strong concern about the drug, and wrote a letter directed at F.D.A. officials to advise against its approval. He, along with many other experts and political figures, foresees wide abuse of the drug, and a higher tally of opioid overdose-related deaths that has risen to over 40,000 in the past year. Personally, he has witnessed doctors, students, and healthcare providers overdose on an intravenous form of sufentanil and has attempted to resuscitate a number of individuals, yet the drug is so potent that even a single injection may be fatal within moments after its release into the body. Clearly, there is a high degree of risk associated with the approval of such a drug in markets. Although its previous presence in hospitals may signal potential benefits, Dsuvia is a drug that warrants close monitoring and an assessment of its true necessity.
However, in light of this, the Food and Drug Administration recently approved Dsuvia, a tablet form of sufentanil that is ten times stronger than fentanyl, a common drug used in hospitals for pain relief that is already heavily abused to contribute to tens of thousands of overdose deaths in past years. The F.D.A. saw the potential of the drug in hospitals, surgical centers, and other supervised medical facilities that may suitable uses for the drug, and perhaps even for wounded soldiers in combat that need a strong therapy delivered very rapidly. And in order to keep it from accelerating the opioid epidemic that has plagued the United States, the drug will be kept within the confines of a supervised medical facility, away from retail pharmaceutical markets and in the privacy of an individual’s home. Additionally, the F.D.A. may require post-market research studies to assess whether the drug produces more benefit than harm and whether it is deemed necessary in a medical setting, considering its potency and its potential for abuse. The makers of the drug, AcelRx, will also keep close measures on its proper distribution and use after it is released on the market next year to ensure that it’s used safely and contributes to better medical operations.
Despite these precautions, there is widespread controversy regarding the approval of this drug. Even the F.D.A.’s advisory committee chairman, Dr. Raeford Brown, expressed strong concern about the drug, and wrote a letter directed at F.D.A. officials to advise against its approval. He, along with many other experts and political figures, foresees wide abuse of the drug, and a higher tally of opioid overdose-related deaths that has risen to over 40,000 in the past year. Personally, he has witnessed doctors, students, and healthcare providers overdose on an intravenous form of sufentanil and has attempted to resuscitate a number of individuals, yet the drug is so potent that even a single injection may be fatal within moments after its release into the body. Clearly, there is a high degree of risk associated with the approval of such a drug in markets. Although its previous presence in hospitals may signal potential benefits, Dsuvia is a drug that warrants close monitoring and an assessment of its true necessity.
Uncovering Health Disparities
-Yifeng (Ethan) Wang
Consider the case of Jalen Hayre (Miller). Jalen was only a toddler when he moved with his mother into an apartment located in the Smith Hill neighborhood of Providence, Rhode Island. The building was antiquated, and there Jalen was exposed to high levels of lead present in the paint. His mother noticed behavioral changes in Jalen, but it was not obvious that Jalen was suffering from lead poisoning. At that time in 1995 not much was known about lead poisoning and there was not the level of awareness seen today. Fortunately, Jalen’s pediatrician’s office detected the lethal levels of lead in his blood and he was immediately treated. However, the lead afflicted irreversible damage to Jalen’s brain (Miller).
As many of you may know already, lead poisoning is not a thing of the past. At the start of 2016, President Obama issued a state of emergency in Flint, Michigan, almost a year after high levels of lead were reported in one resident’s water. It was only the end of July of this year when it was announced by Michigan’s Department of Environmental Quality that over 99% of Flint schools water samples met the 5 parts per billion (ppb) bottled water standard (Michigan DEQ).
Neighborhoods with large communities of color or impoverished communities in America, like Flint, are more likely to be affected by damaging environmental exposures (Miller) than Caucasian, middle-upper class neighborhoods. This leads to differences in health outcomes of different populations, also known as health disparities. As medical professionals, it is important to recognize these health disparities because they make preventable conditions like lead poisoning a reality for patients. Only by recognizing that there is a problem of health disparities can we begin to address change in the factors that lead to health disparities.
Back in Rhode Island, a report in 2011 by the Rhode Island Department of Health shows that the percentage of children whose blood tested positive for blood poisoning has dropped (Childhood Lead). Data from the past years have also shown a decrease in the number of new cases of lead poisoning in RI. However, an interesting finding is that the 2011 report also states that: “Approximately 50% to 60% of blood lead records collected from laboratories and hospitals in Rhode Island fail to report race and ethnicity” for children being tested for blood poisoning (CHILDHOOD LEAD). While the data is separated by town, there was not enough data to be presented by race/ethnicity. This homogenization of data can make it more difficult to identify and address health disparities, and shows that progress still needs to be made.
As many of you may know already, lead poisoning is not a thing of the past. At the start of 2016, President Obama issued a state of emergency in Flint, Michigan, almost a year after high levels of lead were reported in one resident’s water. It was only the end of July of this year when it was announced by Michigan’s Department of Environmental Quality that over 99% of Flint schools water samples met the 5 parts per billion (ppb) bottled water standard (Michigan DEQ).
Neighborhoods with large communities of color or impoverished communities in America, like Flint, are more likely to be affected by damaging environmental exposures (Miller) than Caucasian, middle-upper class neighborhoods. This leads to differences in health outcomes of different populations, also known as health disparities. As medical professionals, it is important to recognize these health disparities because they make preventable conditions like lead poisoning a reality for patients. Only by recognizing that there is a problem of health disparities can we begin to address change in the factors that lead to health disparities.
Back in Rhode Island, a report in 2011 by the Rhode Island Department of Health shows that the percentage of children whose blood tested positive for blood poisoning has dropped (Childhood Lead). Data from the past years have also shown a decrease in the number of new cases of lead poisoning in RI. However, an interesting finding is that the 2011 report also states that: “Approximately 50% to 60% of blood lead records collected from laboratories and hospitals in Rhode Island fail to report race and ethnicity” for children being tested for blood poisoning (CHILDHOOD LEAD). While the data is separated by town, there was not enough data to be presented by race/ethnicity. This homogenization of data can make it more difficult to identify and address health disparities, and shows that progress still needs to be made.
Is Cancer Within Everyone?
-James He
For the most part, cancer is a dreaded disease that we never hope to encounter in our own lives. Yet, in the last couple decades, the disease has grown widespread and serves as a leading cause of death worldwide. The disease is characterized by a plethora of mutations, either genetic or somatic, that ultimately contributes to uncontrolled cell proliferation and the development of an abnormal congregation of cells called a tumor. The mutations that underlie the development of a tumor can be very different in nature, depending on the signaling pathways it affects, the prevalence of the mutated gene within an organism, and external factors present at the onset and developmental course of the mutation. Particular mutations that are capable of driving the formation of a tumor after arising in a healthy cell are determined to be oncogenic driver mutations that typically define the molecular signature of a type of cancer. While these driver mutations were commonly thought to be absent from healthy individuals and could be prevented with the maintenance of a healthy lifestyle, what if I told you that a large portion of cells in any healthy individual may carry a slew of driver mutations that allow a cell to grow faster than others?
Recently, cancer researchers have investigated the prevalence of cancer-driving mutations within the cells of healthy individuals to better understand how such mutations rise. When analyzing the genomes of tumor and healthy cells, very rare mutations that may characterize a tumor can often go undetected due to the sheer volume of genomic data that is necessary to generate a comprehensive profiling of the mutations present within the genomes. Recent developments have allowed researchers to detect such rare mutations that would previously go unnoticed. Dr. Inigo Martincorena of the Wellcome Sanger Institute in Cambridge, England and other researchers have taken advantage of the new technology to more closely examine epithelial and esophageal cells. Upon analysis of 234 biopsies, Dr. Martincorena and his research team found that mutations characteristic of cancer genes were prevalent in approximately one-fourth of the healthy skin cells as well, and promote quicker cell proliferation. In addition, they also examined esophageal cells in an attempt to understand the mutations present in cells inside the body. From nine healthy esophagus samples, they found that mutations were less common and slower to emerge in the esophagus tissue. However, their emergence continues to induce accelerated cell growth, and repeated divisions of these mutated cells will generate mutant clones within the tissue. Over time, these clones may develop more dense populations within the tissue, as Dr. Martincorena asserts, “These mutant clones colonize more than half of your esophagus by middle age.”
While such an idea is terrifying, the presence of a mutation doesn’t directly equate to a malignant tumor. Different factors will contribute to the generation of a malignant tumor, and can vary from individual to individual. However, these recent developments illustrate that a wide plethora of mutations can exist within a healthy individual, and understanding their development as well as their tendency to develop into cancerous tumor cells will provide a novel approach to the study of cancer as a whole. Perhaps mutated cells of different types compete for survival within the body, and only cells that reach a particular malignancy will give rise to cancer.
Recently, cancer researchers have investigated the prevalence of cancer-driving mutations within the cells of healthy individuals to better understand how such mutations rise. When analyzing the genomes of tumor and healthy cells, very rare mutations that may characterize a tumor can often go undetected due to the sheer volume of genomic data that is necessary to generate a comprehensive profiling of the mutations present within the genomes. Recent developments have allowed researchers to detect such rare mutations that would previously go unnoticed. Dr. Inigo Martincorena of the Wellcome Sanger Institute in Cambridge, England and other researchers have taken advantage of the new technology to more closely examine epithelial and esophageal cells. Upon analysis of 234 biopsies, Dr. Martincorena and his research team found that mutations characteristic of cancer genes were prevalent in approximately one-fourth of the healthy skin cells as well, and promote quicker cell proliferation. In addition, they also examined esophageal cells in an attempt to understand the mutations present in cells inside the body. From nine healthy esophagus samples, they found that mutations were less common and slower to emerge in the esophagus tissue. However, their emergence continues to induce accelerated cell growth, and repeated divisions of these mutated cells will generate mutant clones within the tissue. Over time, these clones may develop more dense populations within the tissue, as Dr. Martincorena asserts, “These mutant clones colonize more than half of your esophagus by middle age.”
While such an idea is terrifying, the presence of a mutation doesn’t directly equate to a malignant tumor. Different factors will contribute to the generation of a malignant tumor, and can vary from individual to individual. However, these recent developments illustrate that a wide plethora of mutations can exist within a healthy individual, and understanding their development as well as their tendency to develop into cancerous tumor cells will provide a novel approach to the study of cancer as a whole. Perhaps mutated cells of different types compete for survival within the body, and only cells that reach a particular malignancy will give rise to cancer.
High Cholesterol and Heart Disease: A Problem Only Money Can Solve?
-James He
With the ever-expanding wealth of technology available in modern times, new discoveries are constantly occurring, and drug development is a prime example. Recently, a new class of drugs called PCSK9 inhibitors has proven incredibly effective at lowering cholesterol levels, as well as reducing the risk of heart attacks and strokes that commonly accompany high cholesterol levels. For individuals with a genetic predisposition to such conditions, such as those with familial hypercholesterolemia, the new class of drugs appear to be well-suited to alleviate many of their health issues, and medical experts were extremely hopeful for the tremendous impact these PCSK9 inhibitors could produce. Yet, there’s one huge caveat: the cost.
Like many drugs, the PCSK9 inhibitors are extremely expensive for a number of reasons. High cholesterol and heart disease are problems that as many as ten million Americans struggle with. Unfortunately, improving such health conditions isn’t something a single dose of a drug can fix; individuals recommended to take the drug would require continuous dosage throughout their lifetime. Taking these two factors into account, annual estimates for the cost of widespread distribution of the drug are staggering, from a low of $21 billion to a ceiling of $113 billion. While health improvements are a priceless commodity for affected individuals, insurance companies are more hesitant to cover such costs. Large insurance companies such as Cigna have developed extensive screening measures before administration of the drug, including lengthy pre-authorization forms as well as a patient’s medical records as proof of necessity for the drug. These measures often require very specific information regarding past measures taken toward health improvement. If a patient had changed physicians frequently in the past, acquiring such documentation can be impossible, and the meticulous nature of the whole process can deter a physician’s motivation to acquire such drugs for a patient. As such, even obtaining the drug can often take months, and affected patients are left waiting with little control over the process.
In some cases, the drug may be taken away from a patient after starting medication, as insurance companies will request proof that the drug is eliciting the benefits it is designed to produce. Another round of authorization will start as the patient’s health takes a toll. In response to widespread complaints, insurance companies are starting to recognize the extensive hurdles that patients need to overcome to obtain the medication they may be dependent upon, and are adjusting their policies to accommodate. Companies like Express Scripts and Harvard Pilgrim are attempting to simplify and condense the authorization procedure. Though more companies might follow suit, it is evident that there still is a large population of individuals that are neglected in the process. This entanglement of business and healthcare will continue to persist as technology continues to revolutionize modern society, and opening the lines of communication between producers and consumers will continue to be a major focus.
Like many drugs, the PCSK9 inhibitors are extremely expensive for a number of reasons. High cholesterol and heart disease are problems that as many as ten million Americans struggle with. Unfortunately, improving such health conditions isn’t something a single dose of a drug can fix; individuals recommended to take the drug would require continuous dosage throughout their lifetime. Taking these two factors into account, annual estimates for the cost of widespread distribution of the drug are staggering, from a low of $21 billion to a ceiling of $113 billion. While health improvements are a priceless commodity for affected individuals, insurance companies are more hesitant to cover such costs. Large insurance companies such as Cigna have developed extensive screening measures before administration of the drug, including lengthy pre-authorization forms as well as a patient’s medical records as proof of necessity for the drug. These measures often require very specific information regarding past measures taken toward health improvement. If a patient had changed physicians frequently in the past, acquiring such documentation can be impossible, and the meticulous nature of the whole process can deter a physician’s motivation to acquire such drugs for a patient. As such, even obtaining the drug can often take months, and affected patients are left waiting with little control over the process.
In some cases, the drug may be taken away from a patient after starting medication, as insurance companies will request proof that the drug is eliciting the benefits it is designed to produce. Another round of authorization will start as the patient’s health takes a toll. In response to widespread complaints, insurance companies are starting to recognize the extensive hurdles that patients need to overcome to obtain the medication they may be dependent upon, and are adjusting their policies to accommodate. Companies like Express Scripts and Harvard Pilgrim are attempting to simplify and condense the authorization procedure. Though more companies might follow suit, it is evident that there still is a large population of individuals that are neglected in the process. This entanglement of business and healthcare will continue to persist as technology continues to revolutionize modern society, and opening the lines of communication between producers and consumers will continue to be a major focus.