ABTA RESEARCH COLLABORATION GRANTS
Justin Lathia, PhD and Joshua Rubin, MD, PhD
Identifying sex differences in intrinsic and extrinsic mechanisms in GBM
Advances in medicine emerge from prospective clinical trials, which allow patients with a given disease and meeting specific eligibility criteria to access studies that provide a controlled assessment of a therapy. This eligibility practice, while controlled, has largely ignored the possibility that female and male patients with glioblastoma, a highly malignant form of brain cancer, differ in incidence rates and outcome. In the present era of Precision Medicine, sex of the patient, which is linked to incidence and survival, is not used to personalize care for glioblastoma. Our preliminary and published studies uncovered a remarkably better response to standard care in female glioblastoma patients than in male patients as well as sex-specific differences in signaling networks and interactions in the tumor microenvironment. In this project, we will utilize animal models that allow us to distinguish between the contribution of sex hormones and that of sex chromosomes to determine changes in signaling pathways and alterations in microenvironmental interactions by using a real-time in vivo imaging platform. Our studies will demonstrate a paradigm for sex-specific approaches to personalized medicine in glioblastoma. Progress in our studies will establish a model approach for future studies that take into account sex as a biological variable in cancer care.
BASIC RESEARCH FELLOWSHIPS
Javier Ganz, PhD
Precancer Mutations in Normal Brain: Implications for Oncogenesis and Diagnosis
Understanding how brain cancer starts requires studying the brains of normal people, and trying to figure out where and how the earliest mutations arise that might lead to cancer years later. Our preliminary data suggest that young healthy people already harbor cells in their brain showing mutations that we know drive brain cancer. How do these early mutations arise? Such somatic mutations can be acquired during prenatal development or later in life, but are usually not inherited from the parents. Acquisition of these mutations by normal cells can lead to microscopic abnormalities starting years before detectable tumors appear. By studying the occurrence of early cancer mutations in normal brains, we will establish a roadmap of early-occurring processes that precedes cancer initiation. Brain tumors in general are derived mostly from glial cells, astrocytes and oligodendrocytes, but not neurons. We developed a method that, for the first time, is able to study the complete genome of glial cells and see how they accumulate somatic mutations, starting from fetal life and through older stages. By studying this at the single cell level, will give us a unique opportunity to obtain information with unprecedented resolution, no attainable by any other means. This research will be the first of its kind, improving our understanding of brain tumor initiation but also in providing the basis for developing sensitive methods for detecting incipient tumors where no manifestation is evident.
Albert Kim, MD
Noninvasive tools to study brain metastasis resistance to immunotherapy
Brain metastases (BM) are the most common tumor within the brain and carry a poor prognosis due to limitations in current treatment options. This is a critical unmet need, as the incidence of BM is rising as treatment for systemic cancer improves. Recent promising studies demonstrate that immune checkpoint inhibitors (ICI) can induce objective intracranial response. This response is unpredictable and often not durable. Further compounding this conundrum is the difficulty in accurately assessing response, as an increase in contrast enhancement on standard post-contrast MRI can be seen in treatment-related changes and true tumor progression. These challenges highlight the need for noninvasive biomarkers that reflect the biological response to ICI, as it is not feasible to obtain serial brain biopsies to understand why some patients benefit and others do not. Here, we leverage two novel, complementary approaches – perfusion MRI and circulating tumor DNA from blood and CSF – to understand the longitudinal changes within the tumor environment as a result of ICI. Our proposal is an unprecedented opportunity specifically tailored to patients with BM in which we will obtain detailed tumor blood vessel changes and the genomic basis for such changes during treatment. We seek to identify reasons why ICI ultimately fail, and specific patterns that predict response to ICI. This will result in optimization and better patient selection for these promising treatments.
Thi Thu Trang Nguyen, PhD
LXR Agonists combined with BH3-mimetics as a Novel Treatment for Glioblastoma
Glioblastoma is the most common primary brain tumor with a current life expectancy of 12-15 months. In this proposal, the applicants propose a novel treatment strategy for glioblastoma. Using preclinical models, the investigators are evaluating a combination therapy of two clinically validated drug compounds, BH3-mimetics as well as a certain class of cholesterol lowering compounds that were recently shown to be efficacious in model systems of GBM. We are studying the mechanism by which this drug combination works, which has informed and led us to the proposed strategy. Using the most advanced model system resembling human disease, we will be studying this drug combination in “patient-derived xenograft” model systems. The results of these studies will allow us to propose clinical studies, involving this novel drug combination. In this context, it is noteworthy that both compounds have already entered clinical testing, enabling quicker access to patient application.
Jan Remsik, PharmD, PhD
Immunological determinants of metastatic colonization of leptomeninges
Leptomeningeal metastasis (LM) or spread of cancer cells into the spinal fluid is increasingly common and results in rapid neurologic disability and death. Colonization of leptomeningeal space by cancer cells can take years or even decades after primary cancer diagnosis. The molecular basis of this process remains virtually unknown. Working from our observations from patient samples and unique experimental mouse models, we will dissect the mechanism of cancer cell entry to the spinal fluid using cutting-edge technologies. Moreover, the presence of fully functional immune system in our novel syngeneic mouse models enables us to target immune pathways essential for development and progression of LM. Our approach will rationalize the application of immune therapies, employing the patient’s own immunity as an active weapon against disseminated cancer cells.
Anh Tran, PhD
Tissue factor as a regulator of receptor tyrosine kinases in glioblastoma
Glioblastoma (GBM) is an aggressive form of brain cancer with no cure and few treatment options. Increased activation of receptor tyrosine kinases (RTKs), especially epidermal growth factor receptor, (EGFR) has been well-characterized in GBM. However, drugs that only targeting RTKs have limited efficacy on GBM patients. Our preliminary data show that tissue factor (TF), a protein normally involved in blood clotting, is increased in GBM and can activate many RTKs, even with RTK inhibitor treatment. TF does this through another protein called protease-activated receptor 2 (PAR2), and we found that we could block TF and PAR2 with drugs to decrease GBM malignancy. Furthermore, blocking these proteins also suppress brain tumor-initiating cells, which were known to cause therapeutic resistance and recurrence in GBM. In this study, we will: 1. Investigate how TF and PAR2 interact with and activate RTKs, with the goal to understand how they can help GBM tumors to evade treatments. 2. Determine how TF and PAR2 promote brain tumor initiating cells and test if this effect could be blocked by getting rid of either protein. We will also find the connection between TF, PAR2, RTKs, and tumor-initiating cells. This research will reveal novel targets for GBM therapy and extend our knowledge on the regulation of different factors that contribute GBM malignancy.
Maria Garcia Fabiani, PhD
Impact of H3G34R mutation in reprogramming the glioma immune microenvironment
This project relates to a sub-type of pediatric malignant glioma (pHGG) that is currently incurable. This tumor is found predominantly in the adolescent population and patients have a median survival of 18 months post diagnosis. The extrapolation of tested chemotherapeutics and targeted agents from adult HGG failed to improve the clinical outcome in the pediatric population, so the availability of a reliable experimental model is imperative for the testing of new therapies specifically designed for this type of tumor. The experiments proposed will shed light on many aspects of the tumor’s biology. We are interested in studying: 1) the role that the immune system plays in tumor progression and malignancy 2) and how we could harness it to test therapeutic modalities. To achieve this, we have developed a pHGG mouse model that mirrors the human disease and is a valuable tool to complete the proposed experiments. Having a mouse model to study this disease will allow us to explore many aspects of this type of tumor and possible therapies. The lab where I work has a strong background in brain cancer research and immune-therapeutics of cancer and offers an extraordinary working environment that will allow me to unravel key aspects of this tumor which currently remain unknown. We expect to provide compelling evidence to gain new insights on the biology of this subtype of pHGG which will lead to the development of novel immune-mediated targeted therapies.
Christian Badr, PHD
Therapeutic Targeting of Endoplasmic Reticulum Proteostasis in GBM
Glioblastoma is an aggressive, incurable type of brain tumors enriched in a subset population of glioma cancer stem cells (GSCs) with self-renewal and tumor initiation capacities. We have recently established that Stearoyl CoA Desaturase 1 (SCD1), an enzyme involved in lipid metabolism and fatty acid processing, is essential for GSCs proliferation, tumor initiation and progression. Increased activity of SCD1 protects GSCs against stress conditions thus favoring survival and proliferation, while genetic or pharmacological targeting of this enzyme achieves a potent therapeutic efficacy in brain tumor mouse models.
Our proposed studies seek to:
1) Determine the efficacy and safety of SCD1 inhibitors in combination with standard GBM therapies.
2) Investigate the impact of dietary supplementation with defined fatty acids on GBM tumor progression and response to therapy.
These studies will improve our understanding of a potential impact of fatty acids on brain tumors and will determine whether SCD1-targeting therapies should be evaluated in GBM patients.
Lohitash Karumbaiah, PHD
Immunosensing Glioblastoma Induced Glycomodulation
Glioblastoma (GBM) is the most rapidly growing and commonly occurring form of brain cancer in adults and has the lowest survival rate of all brain cancers. Surgical tumor resection followed by chemical and radiation treatment marginally prolongs patient survival. However, cancer stem cells that spread out from the original tumor into other brain regions become resistant to these treatments, often contributing to tumor recurrence. There are no effective treatments and GBM patients rarely survive longer than a year after diagnosis. Evidence from animal and human studies suggest that aberrant signaling of sugars in the protein meshwork surrounding GBM could promote the maintenance and spreading of cancer stem cells and mediate acquisition of resistance to drugs and novel cell therapies. There are currently no treatments targeting these mechanisms.
We hypothesize that dysregulation of sugars in the tumor microenvironment contributes to GBM progression and suppression of the immune system. In order to test this hypothesis, we will use novel brain tumor-on-chip platforms to recreate the tumor microenvironment and investigate
1) Tumor migration and spread in 3D tumor tissue mimicking scaffolds; and
2) Mechanisms by which tumor cells suppress immune cell activity.
If successful, these studies could help develop novel approaches to therapeutically target and block the activity of sugars surrounding GBM and prolong survival by making the tumor more accessible to current treatments.
Maryam Rahman, MD, MS, FAANS
A Vaccine Strategy to Overcome Treatment Induced Immunosuppresion in Glioma
Patients with glioblastoma are treated with a chemotherapy drug called temozolomide. We have discovered that standard dose temozolomide causes dysfunction of the immune system and prevents efficacy of immunotherapy. This immune dysfunction can be avoided if temozolomide is given in smaller doses over a more prolonged period of time (metronomic dosing). This project will evaluate the cause and duration of immunosuppression in patients with glioblastoma. This research will also determine the utility of using vaccines to reverse immune exhaustion in patients with glioblastoma to improve response rates to immunotherapy.
Yiping He, PhD
Repurposing Remyelination Drugs for Oligodendroglioma Therapeutics
Oligodendrogliomas (ODs) begin as low grade tumors, but uniformly progress to become high grade, aggressive cancers. We aim to devise a non-toxic approach to mitigate such a progression. OD cells originate from progenitor (immature) cells of oligodendrocytes. Our study has revealed that in ~50% of OD patients, tumor cells display features of abnormal immature cells, which undergo uncontrolled proliferation (i.e., tumor progression). This is in contrast to normal cells that differentiate to become non-proliferative, functional oligodendrocytes. Coincidently, in Multiple Sclerosis (MS), defective differentiation of immature cells is a barrier to effective remyelination. As a result, extensive research has been conducted aiming to achieve therapeutic remyelination via promoting such immature oligodendrocytes to differentiate into functional, myelinating cells. Taking advantage of available therapeutic agents developed for this purpose, we have identified agents that can induce OD cells to differentiate. Among them, the most intriguing is Clemastine, an allergy relief medicine. The therapeutic efficacy of Clemastine has been proven in MS patients. We will devise a regimen for inducing OD cell differentiation, using Clemastine as a prototypic drug. The project will potentially lead to a novel treatment for ODs by repurposing commonly used, low toxicity medicines.
Wen Jiang, MD, PhD
Bridging innate and adaptive GBM immunity via phagocytosis checkpoint blockade
Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. The current treatment paradigm is ineffective and carries significant toxic side effects. Increasingly, there is a growing of harnessing the power of the immune system to fight GBM. Our body’s immune system is composed of two main branches. The adaptive branch generates immune memory to prevent disease recurrence after an initial exposure. Adaptive immune cells usually stay dormant but become “activated” in the event of an ”attack”. In contrast, cells of the innate immune system are always on high alert. They are the first defenders of any pathogenic infection or malignant transformation. However, cancers such as GBM has developed the ability to escape from both branches of the immune system, which allows them to grow, spread and disrupt critical biological functions within the body. The goal of the present study is to eliminate GBM by developing a novel bispecific antibody that simultaneously blocks two molecules highly expressed in GBM and responsible for its immune evasiveness. We will: 1) Characterize the bispecific antibody’s ability to generate anti-GBM immune responses. 2) To investigate whether restoration of innate immune surveillance can boost the power of the entire immune system to eliminate GBM. Successful completion of the study would provide strong rationale for translating the bispecific antibody construct for future clinical trials in GBM.
Christine O’Connor, PhD
Cytomegalovirus oncomodulation of the glioblastoma tumor environment
Glioblastoma (GBM) accounts for ~80% of malignant gliomas annually in the US. GBM patient prognosis is poor, and even with treatment, survival is a dismal 12-15 months. This is partly due to the cancer stem cells (CSCs) within the tumor that are refractive to treatments, allowing these cells to continually expand and the tumor to regrow. Thus, novel therapies and a better understanding of the GBM tumor environment are necessary. Emerging data suggests the role for a human herpesvi¬rus, human cytomegalovirus (HCMV), in promoting the acceleration of these tumors. However, the exact mechanism(s) by which HCMV alters the GBM tumor environment remains unknown. The HCMV-encoded G-protein coupled receptor (GPCR), US28, activates many cellular signaling pathways that contribute to GBM progres¬sion. Our findings show US28 drives GBM cells towards the CSC phenotype, thus expanding the population of cells that promote tumor regrowth and recurrence. The goal of our proposal is to gain a better understanding as to how US28 modulates the GBM tumor environ¬ment. US28 is an attractive therapeutic target, as over 2/3rd of FDA-approved drugs target GPCRs. Thus, successful completion of this project will reveal US28-mediated pathways that promote tumor growth, thereby allowing us to leverage cur¬rently approved therapies to prevent GBM CSC expansion. This would prove a novel, paradigm-shifting approach to treating GBM, thus improving patient well-being and outcomes.
Min Tang-Schomer, PhD
Microcircuit Platform to Screen Ion Channel Blockers for Medulloblastoma
Medulloblastoma (MB) is the most common malignant brain tumor in children. The tumors are often subdivided into four groups that define treatment and prognosis. Groups 3 and 4 are the most likely to recur after treatment and patients with these types have the worst outcomes. Our collaborator recently used computational techniques to identify FDA-approved drugs that could be repurposed to treat these malicious tumors. They identified digoxin as a likely candidate and confirmed its antitumor activity in mouse models of MB. However, the mechanism behind digoxin’s tumor killing activity is unclear. Digoxin blocks important ion pumps in cells and may have broad effects on cell viability. Therefore, a better understanding of its mechanism of action is needed before it can be seriously considered as a potential treatment for MB. In this proposal, we will use a novel cell culture system to grow medulloblastoma cells from patients and apply electrical currents to the cells to activate ion channels. We will then apply digoxin and 5 other ion channel blockers to the cultures and monitor mechanisms by which they effect tumor cell growth. These drugs are chosen base on their ability to enter the brain from the bloodstream, their specificity for neurons, and their safety (based on FDA-approval). Therefore, we anticipate that the results from these experiments will be the first step toward identifying new treatments for this devastating pediatric cancer.
Lee Wong, PhD
An investigation of telomere maintenance mechanism in ATRX mutant gliomas
Telomeres are the stretches of DNA that protect our chromosomes. Each time a human cell divides, its telomeres become progressively shorter. Eventually, they reach a ‘crisis point’ where the cells stop growing. I will investigate how mutations in ATRX and H3.3 (2 key regulators of telomeres) activate an aberrant telomere-maintenance mechanism in brain cancers to evade the telomere crisis and cell death. This study will identify molecular targets that might be vulnerable to therapeutic interventions in brain cancers.
Zeng-jie Yang, MD, PhD
NeuroD1 dictates tumor cell differentiation in medulloblastoma
Medulloblastoma (MB) is the most common malignant brain tumor in children. Improved strategies to treat MB are urgently needed. “Differentiation therapy” represents a promising approach for tumor treatment, by means of inducing tumor cells to undergo maturation, thereby inhibiting tumor growth. Differentiation therapy is more selective to target tumor cells with less toxicity compared with conventional chemotherapy or radiation regimen. Here we propose to investigate the mechanism for MB cell differentiation, which will provide compelling evidence to support MB treatment by induction of tumor cell differentiation.
JACK & FAY NETCHIN MEDICAL STUDENT SUMMER FELLOWSHIPS
Hasan Alrefai, BS
Institution: The University of Alabama at Birmingham
Mentor: Christopher Willey, MD, PhD
Project: Effects of Myristoylated Alanine-Rich C-Kinase Substrate on Microglial Activation
Tribute: In memory of George Surgent
Glioblastoma multiforme (GBM) is the most common and deadly brain cancer. There are currently no curative treatments available; therefore, there is a need for improved understanding of GBM biology. In this research project, we will work with MED2, a protein therapy that selectively targets and kills the GBM cells responsible for resistance to radiation and chemotherapy, while leaving normal, healthy cells relatively unaffected.
Under normal conditions, GBMs attract microglia to the tumor site and modify their immune function.
- Microglia: Specialized immune cells found in the brain and central nervous system.
Once microglia go to the tumor, the GBM manipulates them to produce growth factors that help the GBM to grow and spread. Little is known about MED2’s effects on microglial recruitment and modification. In this project, we propose to achieve the following aims:
- To investigate MED2’s effects on microglial survival and
- To investigate MED2’s effects on microglial function to block or promote tumor growth.
This study will provide us insight into how MED2 impacts the cells surrounding GBM that help it to grow and spread. Having a more complete understanding of how MED2 works will help us better develop therapies that may one day enter the clinic to improve outcomes in GBM.
Institution: McMaster University
Mentor: Sheila Singh, MD, PhD, FRCS(C), FAANS
Project: Identifying Synergistic Therapies for Pediatric Group 3 Medulloblastoma
Tribute: In honor of Davvy Lila Netchin
Medulloblastoma (MB) is the most common brain cancer in children. Although 75% of affected patients live longer than 5 years after diagnosis, a subset of patients develop secondary cancers that are essentially incurable. Our lab has previously shown these types of MB tumors contain a large number of cancer cells that are similar to stem cells, and therefore resist standard therapies. We aim to better understand how these cells are able to survive through cancer treatment in order to develop new ways to eliminate them.
We have identified a protein, Bmi1, in the MB stem cells that helps them jump-start tumor growth after they have spread to other parts of the central nervous system. When we block the function of Bmi1 in MB preclinical models and then treat with standard therapy, we are able to drastically reduce their cancer. However, the cancer eventually returns.
We have generated a preliminary list of other genes/proteins that work with Bmi1 to keep these tumor cells from being killed by the standard treatment regimen. We now aim to confirm the role of several of these genes/proteins and eventually develop a multi-drug therapy paradigm that can effectively kill these resistant MB cancer cells.
Andy Ding, BA
Institution: Johns Hopkins University School of Medicine
Mentor: Henry Brem, MD
Project: Therapeutic Potential of Multi-CDK Inhibition in Atypical Teratoid/Rhabdoid Tumor
Tribute: In honor of Paul Fabbri
Atypical Teratoid/Rhabdoid Tumor (ATRT) is a rare but highly aggressive brain tumor that is most commonly found in infants and young children. Historically, ATRT has been a difficult cancer to treat, despite efforts with surgery, radiation, and chemotherapy. Even if treatment is successful in eliminating the cancer, ATRT tends to recur at an average time of 6 months after initial treatment. Radiation therapy has been particularly difficult to use for ATRT, due to potential long-term effects on brain development when administered to children younger than 3 years of age. Due to the robust treatment-resistance exhibited by ATRT, patients tend to succumb to their disease at an average time of 12-18 months after diagnosis. Furthermore, since treatments have largely been unsuccessful, there is no current agreement for a standard treatment for ATRT.
Previous studies have shown that ATRT depends on a protein called cyclin D1 for tumor development and growth. Levels of cyclin D1 in ATRT depend on other cellular components called cyclin-dependent kinases (CDKs).
- Cyclin D1 and Cyclin-dependent kinases: Proteins in cells that help control cell division and therefore, tumor growth.
This proposal seeks to evaluate the drug TG02, which inhibits CDKs and has the potential to block the effects of cyclin D1. We propose to study this in three aims:
- To examine the effects of TG02 on ATRT cells using human ATRT cells in culture.
- To study TG02 effects on ATRT tumors in preclinical models.
- To examine the effects of TG02 on sensitization to radiation therapy for ATRT.
Because TG02 has minimal side-effects and may sensitize ATRT cells to radiation therapy, TG02 offers a unique and compelling therapeutic option that addresses crucial obstacles in the treatment of ATRT with radiation and chemotherapy.
Emily Lavell, MHS
Institution: Mayo Clinic in Jacksonville, Florida
Mentor: Hugo Guerrero-Cazares, MD, PhD
Project: Role of Glioma Extracellular Vesicles on the Transformation of Neural Stem Cells
Tribute: Supported by Southeastern Brain Tumor Foundation
Glioblastoma is the most common and aggressive primary brain tumor in adults, with an average survival rate of 14 months after diagnosis. Tumor recurrence is common, due to a combination of treatment resistance and tumor invasiveness. It has been found, in particular, that glioblastomas are more aggressive when they grow in regions of the brain that normally give rise to healthy stem cells. Preliminary evidence from Dr. Hugo Guerrero-Cazares’ lab indicates that communication between brain tumor cells and stem cells via extracellular vesicles (EVs) may contribute to this increased aggressiveness.
- Extracellular vesicles: Small envelopes containing messages, in the form of functional proteins and nucleic acid molecules, that cells use to communicate with other cells.
Therefore, in my project, I will explore the role of EVs by blocking their release out of the cell using a drug called chloramidine. If the use of chloramidine successfully blocks cell-to-cell communication by glioblastoma cells and results in a decreased cancer malignancy, this could lead to a new way to treat patients with GBM and other brain cancers.
Brian V. Lien, MS
Institution: University of California Irvine School of Medicine
Mentor: Daniel Lim, MD, PhD
Project: Dissecting the Molecular Mechanism of lncGRS-1 in Glioblastoma
Tribute: In memory of Katie Monson
Glioblastoma (GBM) is the most common and aggressive primary brain tumor and is rapidly fatal. Radiation therapy is nearly always prescribed for patients with GBM. There is an unmet need for cancer therapies that enhance the therapeutic effects of radiation therapy while minimizing toxicity to normal brain tissue. Using a CRISPR-based strategy and next generation sequencing, we screened thousands of long non-coding RNAs (lncRNAs) expressed in GBM cells, identifying lncGRS-1 as a promising novel drug target.
- CRISPR: A gene editing technology.
- lncRNA: A type of RNA molecule in cells that can control many functions in the cell by regulating the production of other molecules.
Antisense oligonucleotides (ASOs) are used in gene therapy to modify an RNA molecule of interest and are currently FDA-approved for use in neurological diseases.
- Antisense oligonucleotides (ASO): synthetic molecules that can block specified RNA molecules in cells.
We have found that blocking lncGRS-1 using ASOs can slow GBM cell growth without toxicity to normal human brain cells. While there is evidence that lncGRS-1 is a potentially useful therapeutic target, its function and molecular mechanism remain poorly understood. The goal of my proposed summer research project is to understand the mechanism of action of lncGRS-1 at the molecular level by examining a variety of ways that lncGRS-1 may interact with other components of the genome, using gene editing, ASOs, and chromosome conformation capture.
Edith Yuan, BA
Institution: Keck School of Medicine – University of Southern California
Mentor: Frank Attenello, MD
Project: Effects of Silencing Long Non-Coding RNA on the Malignancy of Glioblastomas
Tribute: In memory of Rose DiGangi
Glioblastoma (GBM) is the most common and aggressive brain tumor. Despite current treatments, the prognosis for GBM remains poor, with the average survival rate of 15 months. Treatment for GBM is not only medically challenging, but the disease also brings immense emotional distress to patients and their families. Because of this, our lab is motivated in studying new therapies that will help combat the aggressiveness of GBMs.
Studies have shown that patients with an overabundance of certain lncRNAs tend to have lower rate of survival. Therefore, in this project, I will investigate long non-coding RNAs (lncRNAs) as a potential target for GBM therapies.
- lncRNA: A type of RNA molecule that can control many functions in the cell by regulating the production of other molecules.
The goals of our project are to:
- Study the effects of suppressing specific lncRNAs on tumor cell invasiveness and proliferation (when cells multiply by making copies of themselves).
- Test if an established, pharmacological method of blocking the production of specific RNAs can effectively suppress the lncRNAs that contribute to GBM progression.
We believe that by preventing the expression of specific lncRNAs, there will be a decrease in GBM aggressiveness and thus, an improvement in patient survival.