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CAR-T therapy, a form of immunotherapy that revs up T-cells to recognize and destroy cancer cells, has revolutionized the treatment of blood cancers, including certain leukemias, lymphomas, and most recently, multiple myeloma. However, Black and Hispanic people were largely absent from the major clinical trials that led to the U.S. Food and Drug Administration approval of CAR-T cell therapies.
In a study published today in Blood Marrow Transplantation (BMT), investigators at the National Cancer Institute-designated Montefiore Einstein Cancer Center (MECC) report that Black and Hispanic patients had outcomes and side effects following CAR-T treatment that were comparable to their white and Asian counterparts.
“Representation in cancer clinical trials is vital to ensuring that treatments are safe and effective for everyone,” said Mendel Goldfinger, M.D., co-corresponding author of the paper, a medical oncologist at Montefiore Health System, assistant professor of medicine at Albert Einstein College of Medicine, and member of the MECC Cancer Therapeutics Program. “We couldn’t have been happier to learn that our patients who identify as Black and Hispanic have the same benefits from CAR-T therapy as white patients. We can only begin to say that a cancer treatment is transformational when these therapies benefit everyone who comes to us for care.”
People who identify as Black and Hispanic often have tumor biology, immune system biology, and side effects that are distinct from white people. However, very few minorities were enrolled in the major trials that led the FDA to approve CAR-T cell therapy.
Parity for Black and Hispanic Patients
The new BMT study evaluated outcomes for 46 participants treated at Montefiore between 2015 and 2021. Seventeen of the participants were Hispanic, 9 were African American, 15 were white, and 5 were Asian.
Among Black and Hispanic patients, 58% achieved a complete response after treatment and 19% achieved a partial response. For white and Asian patients, 70% achieved a complete response and 20% had a partial response, indicating no statistical differences among racial and ethnic backgrounds. Results were similar with respect to major side effects experienced: Approximately 95% of participants in each group had mild to moderate cytokine release syndrome, a common side effect to immunotherapy in which people experience fever and other flu-like symptoms.
Diversifying Cancer Clinical Trials
“Our findings demonstrate that we are able to effectively treat people from historically marginalized groups using CAR-T; our hope is that more people from a diverse range of racial and ethnic backgrounds will be included in clinical trials,” said co-author Amit Verma, M.B.B.S., associate director of translational science at MECC, director of the division of hemato-oncology at Montefiore and Einstein, and professor of medicine and of developmental and molecular biology at Einstein. Ira Braunschweig, M.D., associate professor of medicine at Einstein and director of Stem Cell Transplantation and Cellular Therapy and clinical program director, Hematologic Malignancies at Montefiore, is also co-corresponding author on the study.
At Montefiore, approximately 80% of clinical trial participants are minorities, compared with the nationwide figure of only 8%.
“As an academic medical center, it is not enough to make novel therapies like CAR-T available,” said Susan Green-Lorenzen, R.N. M.S.N., system senior vice president of operations at Montefiore and study co-author. “We need to be at the forefront of ensuring that these treatments are effective for the communities we serve — this research reflects this commitment.”
The study is titled “Efficacy and safety of CAR-T cell therapy in minorities.” In addition to Drs. Goldfinger, Verma, and Braunschweig and Ms. Green-Lorenzen, other Einstein and Montefiore authors are Astha Thakkar, M.D., Michelly Abreu, N.P., Kith Pradhan, Ph.D., R. Alejandro Sica, M.D., Aditi Shastri, M.D., Noah Kornblum, M.D., Nishi Shah, M.D., M.P.H., Ioannis Mantzaris, M.D., M.S., Kira Gritsman, M.D., Ph.D., Eric Feldman, M.D., and Richard Elkind, P.A.-C.

Aspirin therapy, as opposed to statin use, for non-obstructive coronary artery disease does not reduce major cardiovascular events, according to a new study published in the journal Radiology: Cardiothoracic Imaging.
Coronary artery disease is the most common type of heart disease, affecting roughly 6.7% of U.S. adults, according to the Centers for Disease Control and Prevention. Coronary artery disease occurs when there is a buildup of plaque in the arteries that supply blood to the heart. Coronary artery disease puts people at a higher risk for major adverse cardiovascular events, including heart attack and death.
Non-obstructive coronary artery disease occurs when there is less than 50% stenosis, or narrowing, of the coronary arteries due to plaque buildup. Coronary CT angiography (CCTA) is often recommended as a first-line test to detect plaque.
Medications called statins are commonly prescribed for patients who are diagnosed with non-obstructive coronary artery disease. Statins reduce the production of low-density lipoprotein (LDL) cholesterol and draw cholesterol out of plaque, therefore stabilizing the plaque and reducing the risk of it rupturing. Aspirin is another drug that is commonly recommended. However, not much research has been done to determine whether aspirin is effective at reducing major cardiovascular events in patients with non-obstructive coronary artery disease.
“While observational in nature, our data calls into question the value of initiating aspirin therapy following the diagnosis of non-obstructive coronary artery disease on a coronary CT angiography,” said study author Jonathan Leipsic, M.D., professor and head of the Department of Radiology at the University of British Columbia in Vancouver, Canada.
For the study, researchers used data from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, a large, multinational database of patients who have undergone CCTA. A total of 6,386 patients (mean age 56.0 years, 52% men) who had either no detectable coronary plaque or non-obstructive coronary artery disease were selected. Patients with obstructive coronary artery disease that had 50% or greater stenosis were excluded. The mean follow-up period for selected patients was 5.7 years.
A total of 3,571 (56%) of the patients included in the study had no plaque and 2,815 (44%) had non-obstructive coronary artery disease. Non-obstructive coronary artery disease was associated with a 10.6% risk of all-cause mortality compared to 4.8% in patients without plaque.
Baseline aspirin and statin use were documented for both groups. In individuals with nonobstructive coronary artery disease, aspirin therapy was not associated with a reduction in major adverse cardiovascular events. Alternatively, statin use was associated with a significant reduction in cardiovascular events, including heart attack and death.
“Our findings build on prior analyses from the CONFIRM registry at 2.3-year follow-up which called into question the utility of aspirin in the setting of CCTA diagnosed atherosclerosis,” Dr. Leipsic said.
Neither aspirin nor statin therapy improved clinical outcomes for patients with no detectable plaque. Aspirin therapy may still be beneficial in cases of high-risk plaque or high plaque burden, Dr. Leipsic said.
“Ultimately, further research is required to determine whether, and at what threshold, clinicians should consider prescribing aspirin for patients upon the identification of non-obstructive coronary artery disease on coronary CT angiography,” he said.

More and more mutations clutter up our DNA as we age. Mostly, these don’t cause problems. But sometimes, a switch will flip, and a mutated cell turns cancerous. Can we see this shift in time to prevent or treat cancer before it starts?
Led by researchers at Fred Hutchinson Cancer Research Center, a scientific team who studies a precancerous condition of the esophagus (called Barrett’s esophagus or BE) are working to answer this question. In work published April 28 in Nature Communications, the team revealed that DNA changes in BE cells that presage esophageal cancer can be spotted years before cancer develops.
The characteristic changes include rearrangements of large chunks of DNA and damage to both copies of a tumor-suppressing gene called TP53.
“Most patients who progressed [to esophageal cancer] had two ‘hits’ [changes that likely inactivate normal gene function] to TP53,” said Dr. Thomas Paulson, a senior staff scientist in the Grady Lab who co-led the project. “Cells with altered TP53 had spread to larger regions of the esophagus and persisted over longer periods of time compared to patients who didn’t progress to cancer.”
Though the team’s ultimate goal is to improve diagnostics and screening for esophageal cancer, Paulson emphasized that this study compares the mutations and DNA changes that occurred in patients who progressed to cancer with those that occurred in patients with stable, benign BE. While the findings are significant and are based on analysis of over 400 tissue samples, results from this 80-patient study would need to be validated in other patient groups before they could be used clinically to predict whether other BE patients will progress to cancer, he said.
Winding back the clock to cancer’s earliest stages
In some people with long-term acid reflux, Barrett’s esophagus arises as a new type of esophageal lining that better resists the damage caused by reflux. Even though it’s often accompanied by DNA mutations, most people will never need treatment for their BE, which will remain benign and stable. But for about 5% of patients with BE, their condition will progress to a kind of cancer called esophageal adenocarcinoma. Though esophageal cancer is relatively rare (about 20,000 new cases are diagnosed each year in the U.S.), it’s aggressive: Only 20% of patients survive five years past diagnosis.

A walkout at New York University’s medical school was held to protest the possible hiring of Dr. David Sabatini, who has been accused of sexual misconduct.Graduate students, faculty and alumni from New York University’s Grossman School of Medicine staged a walkout Wednesday to protest a report that the school may soon hire Dr. David Sabatini, a biologist facing allegations of sexual harassment.At least 200 people stretched across First Avenue in front of the N.Y.U. Medical Center, chanting and holding signs with slogans like “No means no” and “No to Sabatini.” They said they felt betrayed and confused by the possibility that Dr. Sabatini might join their school, which was reported in science.org. “I hope he doesn’t get hired,” said Grant Hussey, a graduate student at the medical school. “The track record is clear.”Dr. David Sabatini has maintained that he had been falsely accused of sexual harassment by a colleague with whom he said he had a consensual relationship.Sylvain Gaboury/Patrick McMullan, via Getty ImagesDr. Sabatini, 54, is a prominent biologist, best known for his discovery of the mTOR protein, which regulates cell growth in animals, as a graduate student. In a statement, he said accusations of sexual misconduct were false and declined to comment on potential employment at N.Y.U.“As I have maintained consistently from the start, I differ sharply with the way this matter has been characterized, and I intend to set the record straight and stand up for my integrity,” Dr. Sabatini said.Last August, Dr. Sabatini was placed on administrative leave at the Massachusetts Institute of Technology, where he ran a research lab through the Whitehead Institute of Biomedical Research, after an investigation into allegations of sexual harassment made against him — conducted by a law firm separate from the university — found he had violated the institute’s sexual misconduct policy.On the same day, Dr. Sabatini also resigned from the Whitehead Institute and was fired by the Howard Hughes Medical Institute, which had been funding his work at M.I.T.He resigned from M.I.T. earlier this month after three faculty members recommended that his tenure be revoked, according to a letter to faculty from L. Rafael Reif, M.I.T. president, and obtained by The Boston Globe.In the letter, Dr. Reif wrote that the faculty members had reviewed the allegations and found that Dr. Sabatini had violated the school’s policy on consensual romantic relationships in the workplace. They also had concerns about his “unprofessional” behavior with lab members.At the protest, Megan Kirchgessner, a postdoctoral fellow at the medical school, said she was disappointed that the school would consider hiring a person facing accusations of sexual harassment when the role could have been offered to someone from an underrepresented background in science.“It was kind of a moment of a cynical reality check,” Dr. Kirchgessner said.Deborah DeLair, a professor at the medical school, said hiring Dr. Sabatini would contradict the school’s policies on sexual misconduct.“The rules should apply to everyone regardless if you’re a well-known researcher,” she said. “You can’t say one thing and then do another.”Several faculty members wrote a letter to the dean and vice dean of the medical school urging them not to recruit Dr. Sabatini. The letter, which was obtained by The New York Times, said that such a move could have a profound impact on the reputation of the school. As of Wednesday, it had been signed by about 90 faculty members.“While we understand there are still legal proceedings in progress and that the public does not yet have all of the facts, we are worried that this hiring would signal a shift in policy that conflicts with our commitment to provide a respectful training environment, a culture of respect for women, and zero tolerance of misconduct,” the letter stated.In a statement, Dafna Bar-Sagi, vice dean of the medical school, said the administration was evaluating the allegations and would not make a hiring decision that would “deviate” from the school’s policies.“We are looking closely at Dr. Sabatini’s case because it is clear that many aspects of his departure from M.I.T. and the Whitehead Institute were never publicly scrutinized,” Dr. Bar-Sagi said. “Moreover, dozens of Dr. Sabatini’s peers and colleagues have shared with us views that are at odds with the investigation and its outcome. That said, we take the concerns we are hearing from our faculty and trainees very seriously.”It was not immediately clear what position Dr. Sabatini was being considered for or what stage the hiring process had reached.In October 2021, Dr. Sabatini filed a lawsuit against the Whitehead Institute and his accuser, a former colleague, claiming that he had been wrongly accused of sexual harassment by the colleague, with whom he said he had had a consensual relationship.The accuser filed a countersuit in December, claiming Dr. Sabatini had coerced her into having sex, that he had created a “toxic and sexually charged lab environment” and that he had “groomed” her while she was still a graduate student being mentored by him.Standing outside N.Y.U. on Wednesday, several medical school students and employees said that if Dr. Sabatini were to be hired, they would not attend his seminars and would avoid any school functions he goes to.“We’re still at the point where we’re hoping we can have our voices heard enough before this actually goes through,” Dr. Kirchgessner said.

A just-published study provides previously unknown answers about which hospitalized COVID-19 patients are most likely to need mechanical ventilation or to die.
Researchers showed that vital signs and lab results at the time of hospital admission are the most accurate predictors of disease severity.
“Our models show that chronic conditions, comorbidities, sex, race and ethnicity are much less important in the hospital setting for early prediction of critical illness,” said Dr. Sevda Molani, lead author of a paper published in the journal Scientific Reports.
Molani and team looked at risk factors based on two age groups of hospitalized patients, one being between 18 and 50 years old and the other being 50 or older, and found that risk factors that lead to severe cases and/or death differ with younger vs. older patients.
For example: Body mass index is a more important predictor of COVID-19 severity for younger patients than for older patients. Many comorbidities such as malignancy, cardiomyopathy and COPD have higher odds ratios for severe outcomes in younger patients than in older patients. For both older and younger patients, vital signs, early hospital laboratory tests and the need for supplemental oxygen are more useful for predicting severe outcomes than comorbidities and demographics.The findings are meaningful in the clinical setting.
“Risk prediction in COVID-19 is complex as the disease course is highly variable between persons, ranging from completely asymptomatic in some people to critical illness or death in others. While age is known to be highly predictive of death, other risk factors within age strata are incompletely explored. This study challenges our dogma that comorbidities are the major drivers of severe outcomes like mechanical ventilation or death in hospitalized patients with COVID-19. Instead, we find that other physiological features that can be measured within one hour of hospitalization more strongly predict who will go on to severe outcomes,” said Dr. Jason Goldman, an infectious disease specialist at Swedish Providence and a member of the study team. “These findings remind the treating clinician to incorporate physiological parameters into risk stratification, and subsequently into decisions on treatment allocations.”
The retrospective study examined the electronic health records of more than 6,900 patients between June 31 and November 15 of 2021. The vast majority of patients hospitalized with COVID-19 — 92 percent of the younger patients and 75 percent of the older patients — had not received COVID-19 vaccination.
Existing risk models for hospitalized patients were developed early on in the pandemic. This research addresses the need for updated models that reflect current standard of care for COVID-19, where fewer uncommon labs are used, and more therapeutic treatment options are available. Future investigations will benefit from finer granularity of subdivisions by age, BMI, and more detailed variables on conditions and drugs that affect individual immune response.
“Chronic medical conditions are still important risk factors for severe COVID-19. However, when a patient has just been admitted to the hospital, their current status can be more helpful in predicting what level of care they are likely to need,” said ISB Assistant Professor Dr. Jennifer Hadlock, corresponding author of the study. “As the standards of care for COVID-19 evolve, our risk models need to evolve with them.”
The collaborative study was conducted by researchers at ISB, Swedish Providence, Onegevity and Mayo Clinic Jacksonville.
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The spinal column is the central supporting structure of the skeleton in all vertebrates. Not only does it provide a place for muscles to attach, it also protects the spinal cord and nerve roots. Defects in its development are known to cause rare hereditary diseases. Researchers from the Ebisuya Group at EMBL Barcelona have now created a 3D in vitro model that mimics how the precursor structures that give rise to the spinal column form during human embryonic development.
The spinal column consists of 33 vertebrae, which form pairs of precursor structures called somites. Somites give rise to not only our vertebrae, but also our ribs and skeletal muscles. To ensure that these structures are formed correctly, somite development is tightly regulated, and each pair of somites arises at a particular sequential time point in development. This process is controlled by the segmentation clock, which is a group of genes that creates oscillatory waves, every wave giving rise to a new pair of somites.
“For the first time, we have been able to create periodic pairs of human mature somites linked to the segmentation clock in the lab,” said Marina Sanaki-Matsumiya, first author of the study published in Nature Communications. Using this approach, the researchers developed a 3D in vitro model of human somite formation, also known as ‘somitogenesis’.
Creating a robust somitogenesis process
The team cultured human induced pluripotent stem cells (hiPSC) in the presence of a cocktail of signalling molecules that induce cell differentiation. Three days later, the cells started to elongate and create anterior (top) and posterior (bottom) axes. At that point, the scientists added Matrigel to the culture mix. Matrigel is what some scientists call the magic powder: a protein mixture that is critical to many developmental processes. This process eventually led to the formation of somitoids — in vitro equivalents of human somite precursor structures.
To test whether the segmentation clock regulates somitogenesis in these somitoids, the researchers monitored the expression patterns of HES7, the core gene involved in the process. They found clear evidence of oscillations, especially when somitogenesis was about to start. The somites that formed also had clear markers of epithelization — an important step in their maturation.
Somite size matters
The Ebisuya group studies how and why we humans are different from other species when it comes to embryonic development. One of the model systems they use to understand interspecies differences is the segmentation clock. In 2020, the group uncovered that the oscillation period of the human segmentation clock is longer than the mouse segmentation clock.
The current study also shows a link between the size of somites and the segmentation clock. “The somites that were generated had a constant size, independently of the number of cells used for the initial somitoid. The somite size did not increase even if the initial cell number did.” explained Sanaki-Matsumiya. “This suggests that the somites have a preferred species-specific size, which might be determined by local cell-cell interactions, the segmentation clock, or other mechanisms.”
To study this further, Miki Ebisuya and her group are now planning to grow somitoids of different species and compare them. The researchers are already working on several mammalian species, including rabbits, cattle, and rhinoceroses, setting up a ‘stem cell zoo’ in the lab.
“Our next project will focus on creating somitoids from different species, measure their cell proliferation and cell migration speed to establish what and how somitogenesis is different among species,” said Ebisuya.
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Materials provided by European Molecular Biology Laboratory. Original written by Carla Manzanas. Note: Content may be edited for style and length.

About one-fifth of often deadly head and neck cancers harbor genetic mutations in a pathway that is key to normal cell growth, and scientists report those mutations, which enable abnormal cancer cell growth, can also make the cancer vulnerable.
Keys to targeting that vulnerability include individualized genomic analysis to identify a patient’s specific mutation, and finding the drugs that directly target it, investigations that should be given more attention in cancer therapy development, they report in a review article in the journal NPJ Genomic Medicine.
The MAPK pathway is a “signaling hub” for cells important to the usual development of the head and neck region, and activating key pathway constituents, like the genes MAPK1 and HRAS, is known to drive the growth of a variety of cancers, says Dr. Vivian Wai Yan Lui, molecular pharmacologist and translational scientist at the Georgia Cancer Center and Medical College of Georgia and the paper’s corresponding author.
But the mutations in the genes in the MAPK pathway that enable tumor growth can also make it sensitive to drug therapy, says Lui. While a lot of discovery is still needed to find more mutations in the MAPK pathway and the drugs that target them, Lui says they are among the most logical treatment targets for this tough-to-treat cancer.
As she speaks, she is looking in her lab for drugs that kill head and neck primary tumors from patients, and at the genetics behind how they kill.
“It’s critical to the survival of the cancer,” says Lui, and every cancer type likely has one or more drug-sensitizing mutations that may vary in individuals depending on how they got cancer.

Lymphomas are blood cancers that often start from lymph nodes. Lymph nodes contain not only hematopoietic cells, mainly B- and T-lymphoid cells, but also non-hematopoietic cells (NHCs), also called stromal cells. We know from previous research that NHCs have an active role in the development of lymphomas. However, it is still not clear how they promote the expansion and proliferation of lymphomas. Despite advancement in therapeutic options, most lymphomas remain uncurable.
In a paper published in Nature Cell Biology in March 2022, researchers from the University of Tsukuba constructed an atlas of more than 100,000 NHCs collected from 27 human samples, encompassing different types of lymphomas such as follicular lymphomas. The research team used single-cell RNA sequencing to profile the gene expression of the hundreds of thousands of NHCs. On the basis of this expression, the researchers divided them into different subgroups, called clusters, and discovered a significant heterogeneity of these cells. The researchers observed that this heterogeneity was detectable also in aggressive lymphomas, meaning that some of these subgroups could be involved in the progression of the tumor. They identified several subgroups of NHCs, including some that were previously unrecognized — for example, specific types of endothelial cells. “Once the atlas was developed, we performed differential gene expression analysis between subgroups in different types of lymph nodes affected by lymphoma,” explains Professor Mamiko Sakata-Yanagimoto, lead author of the study, “and interestingly we found subcluster-specific transcriptional changes and a specific pattern of interaction with malignant cells in the stroma of follicular lymphomas.” Follicular lymphomas are one of the most common types of lymphoma. Therefore, having a gene expression signature and a prediction of how NHCs can interact with malignant cells may be very useful to keep the tumor development under control, as they suggest potential biomarkers for therapeutic approaches.
Another important finding of the study suggested that human lymph nodes have unique NHC subpopulations that have not been previously detected in mouse lymph nodes. This highlights the importance of carrying out more human studies in the future.
Professor Mamiko Sakata-Yanagimoto summarized the contribution of this research by noting its potential for therapeutic applications globally: “This single-cell atlas of NHCs in human lymph nodes that we developed is applicable to lymphoma researchers all around the world. It can provide deep insights into lymphoma stromal biology and resources applicable to future studies on lymphomas, and also identify potential stroma-derived biomarkers that may serve as clinical indicators and/or therapeutic targets.”
This work was supported by Grants-in-Aid for Scientific Research (KAKENHI: JP20J20851 to Y.A., JP21H02945 to M.S.-Y., and JP19H03683 to S.C.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan; AMED under grant numbers JP21ck0106544 and JP21ck0106644 (to M.S.-Y.) and JP21cm0106505 (to S.C.); and Okinaka Memorial Institute for Medical Research, Foundation for Promotion of Cancer Research, and Takeda Science Foundation (to M.S.-Y.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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As Earth’s climate continues to warm, researchers predict wild animals will be forced to relocate their habitats — likely to regions with large human populations — dramatically increasing the risk of a viral jump to humans that could lead to the next pandemic.
This link between climate change and viral transmission is described by an international research team led by scientists at Georgetown University and is published April 28 in Nature.
In their study, the scientists conducted the first comprehensive assessment of how climate change will restructure the global mammalian virome. The work focuses on geographic range shifts — the journeys that species will undertake as they follow their habitats into new areas. As they encounter other mammals for the first time, the study projects they will share thousands of viruses.
They say these shifts bring greater opportunities for viruses like Ebola or coronaviruses to emerge in new areas, making them harder to track, and into new types of animals, making it easier for viruses to jump across a “stepping stone” species into humans.
“The closest analogy is actually the risks we see in the wildlife trade,” says the study’s lead author Colin Carlson, PhD, an assistant research professor at the Center for Global Health Science and Security at Georgetown University Medical Center. “We worry about markets because bringing unhealthy animals together in unnatural combinations creates opportunities for this stepwise process of emergence — like how SARS jumped from bats to civets, then civets to people. But markets aren’t special anymore; in a changing climate, that kind of process will be the reality in nature just about everywhere.”
Of concern is that animal habitats will move disproportionately in the same places as human settlements, creating new hotspots of spillover risk. Much of this process may already be underway in today’s 1.2 degrees warmer world, and efforts to reduce greenhouse gas emissions may not stop these events from unfolding.

In studies using mice grafted with human Ewing sarcoma tissue, researchers from Georgetown University Medical Center and colleagues have identified a biological pathway that is activated when tissue is starved of oxygen due to rapid growth of a tumor, thereby allowing cancer cells to make genetic changes so they can metastasize to the bone and thrive even when exposed to chemotherapy.
The pathway the scientists identified involves a receptor on the surface of a cancer cell, called Y5R, which plays a role in mediating oxygen-deprivation effects — if it was blocked or turned off, genetic changes would be limited, thereby inhibiting metastasis of a tumor.
The finding appeared April 28, 2022, in Nature Communications.
Each year, about 200 children and young adults in the United States are diagnosed with a Ewing tumor. About half of all Ewing sarcoma diagnoses are in people between the ages of 10 and 20; almost all cases of Ewing sarcoma occur in white and Hispanic people. If the tumor has spread to distant areas at the time of diagnosis, the 5-year survival rate is 38 percent but if it spreads to the bone, survival drops to between 8 to 14 percent.
“While the role of rapid genetic changes in spurring the growth of cancer is well known, the mechanisms initiating these changes are not well understood and strategies to prevent them are lacking,” says Joanna Kitlinska, PhD, an associate professor in the Department of Biochemistry and Molecular & Cellular Biology at Georgetown University and corresponding author of the study. “That’s why our identification of Y5R’s involvement in initiating such genetic alterations is important as it gives us a target to aim at or block that could avert cancer genome evolution and resulting progression to metastatic tumors that are resistant to chemotherapy.”
The current standard-of-care for Ewing sarcoma involves systemic cell-killing chemotherapy which can affect all cells in the body leading to side effects. There are no treatments targeted at genetic alterations that are used in routine treatment of Ewing sarcoma, which might make treatments less toxic. In particular, adequate treatments for patients with metastatic disease are lacking.
There are currently a number of drugs available that target Y5R because it’s also implicated in regulating food intake and psychiatric disorders. Several Y5R-targeted drugs have been successfully used in animal studies; one of them was used in human clinical trials for obesity. However, most of them are designed to block functions in the brain that inhibit food intake. According to Kitlinska, the main challenge will be to design Y5R-targeted drugs that do not cross the blood-brain barrier as these effects are undesirable in cancer patients.
“We will keep performing experiments in mice in order to try to identify the mechanisms triggering spread of Ewing to the bone,” says Kitlinska. “Findings in Ewing sarcoma may also be relevant to other cancer types known to have high expression levels of Y5R, including another pediatric cancer, neuroblastoma, as well as common adulthood malignancies, such as breast, prostate and liver cancers.”
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