isbscience.org/research/cancers/We believe the greatest impact in cancer research will come from how cancers are studied vs. which cancers are studied.
Cancer research poses many interconnected complexities related to early detection, stratification and treatment. The cross-disciplinary holistic, integrative nature of systems biology makes ISB researchers well suited to tackle the complexity of these diseases.
ISB’s scientists are focused on a variety of cancer research areas:
Predicting Cancer Therapy
We are developing single cell proteomics and single cell metabolomics methods that, when combined with kinetic studies and statistical physics models, can yield effective cancer treatment strategies for individual patients, and can unveil mechanisms of drug response and resistance.
Cancer Immunotherapy
Researchers utilize single cell methods, coupled with large scale molecular dynamics calculations to develop a molecular-level understanding of patient responses to engineered T cell and drug-based cancer immunotherapies, and to engineer new therapies for the most challenging patients.
Multicellularity
We are seeking to understand the very phenomenon of multicellularity in health and disease because cancer is the price we pay for having evolved a complex multicellular system. The goal is to arrive at a new level of understanding of cancer using the new powerful formal tools of the epigenetic landscape and by considering cell population dynamics.
The Cancer Genome Atlas (TCGA)
TCGA was established to accelerate our understanding of the molecular basis of cancer, ushering in the development of many novel analytical approaches. ISB-led teams have been associated with the TCGA research network for the better part of a decade, developing computational methods that have helped researchers map and analyze cancer on a large scale to gain a deeper understanding of its genetic underpinnings and apply it to diagnostic, treatment and prevention strategies.
Featured Projects
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TCGA Researchers Identify Potential Drug Targets for Leading Form of Deadly Liver Cancer
ISB researchers and colleagues from TCGA Research Network performed the first large-scale, multi-platform analysis of hepatocellular carcinoma, the predominant form of liver cancer. Such integrated analyses enabled the identification of potential therapeutic targets and facilitated biological insights that would not have been possible otherwise.
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A Cell-Surface Membrane Protein Signature for Glioblastoma
Using integrated protein and gene expression data, ISB researchers developed a 33-gene signature for glioblastoma, an aggressive form of brain cancer.
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Novel clustering algorithm identifies functional mutations in cancer genes
In a study published in PLoS Computational Biology, researchers at Institute for Systems Biology (ISB) have developed a multiscale mutation clustering algorithm (M2C) that identifies variable length regions with high mutation density in cancer genes.
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Stitching Together Insight For Deadly Brain Cancer Glioblastoma
Using data from TCGA and ENCODE, ISB researchers developed an integrative database and analysis platform that provides insight into the underpinnings of glioblastoma multiforme, and identified a never before seen association between increased levels of immune molecules, tumor immune cell infiltration, and decreased patient survival.
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Integrative Study of Rare Adrenocortical Carcinoma Reveals Prognostic Molecular Subtypes
Adrenocortical carcinoma (ACC) is a rare endocrine cancer with limited therapeutic options and overall poor outcome. In TCGA (The Cancer Genome Atlas) research published on May 9, 2016, in the journal Cancer Cell, scientists, including several from Institute for Systems Biology, comprehensively analyzed 91 ACC specimens from four continents using state-of-the-art genomic technologies and computational methods. The goal of the study was to identify additional oncogenic alterations to provide a framework for further research and guide development of therapies.
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Prostate Cancer Study Identifies Numerous Subtypes of the Disease
Prostate cancer is the second most common cancer in men worldwide. The clinical behavior of prostate cancer is variable with some men exhibiting indolent prostate cancer which can be monitored over time while other men develop aggressive prostate cancer which can lead to metastasis and death.
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A Multilevel Pan-cancer Map Links Gene Mutations to Cancer Hallmarks
In the scientific community, cancer is not considered a single disease but a multitude of diseases. Different genes and molecular pathways have been associated with different types of cancer. These differences at the molecular level are being leveraged to enable personalized treatment regimes for cancer patients.
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Cancer Genomics Cloud
The ISB Cancer Genomics Cloud:
Leveraging Google Cloud Platform for TCGA Analysis
The ISB Cancer Genomics Cloud (ISB-CGC) is one of three pilot projects funded by the National Cancer Institute with the goal of democratizing access to the TCGA data by substantially lowering the barriers to accessing and computing over this rich dataset. The ISB-CGC is a cloud-based platform that will serve as a large-scale data repository for TCGA data, while also providing the computational infrastructure and interactive exploratory tools necessary to carry out cancer genomics research at unprecedented scales. The ISB-CGC will also facilitate collaborative research by allowing scientists to share data, analyses, and insights in a cloud environment. -
A Mixture of Markers from Two Distinct Cell Types Indicates Poor Prognosis in Breast Cancer
Metastatic breast cancer remains an incurable disease and has stimulated the search for the most aggressive cell types in the tumors that drive metastasis. These cells have long been thought to possess stem-cell character, hence the idea of Cancer Stem Cells, or CSCs.
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How Physics and Thermodynamics Help Assess DNA Defects in Cancer
‘Big data’ cancer research has revealed a new spectrum of genetic mutations across tumors that need understanding.
Existing methods for analyzing DNA defects in cancer are blind to how those mutations actually behave.
ISB scientists developed a new approach using physics- and structure-based modeling to systematically assess the spectrum of mutations that arise in several gene regulatory proteins in cancer. -
New Details on Thyroid Cancer May Lead to More Precise Therapies
Papillary thyroid cancer represents 80 percent of all thyroid cancer cases.
Integrative analysis resulted in the detection of significant molecular alterations not previously reported in the disease.
ISB researchers identified microRNAs which may lead to more precise therapy. -
New Structural Map Helps To Understand Aggressive Tumors
Aggressive tumor growth is linked to high activity of a macromolecular assembly called RNA polymerase I.
ISB and FHCRC researchers collaborate to map the architecture of the assembly using a powerful crosslinking-mass spectrometry (CXMS) technology.
Structural maps provide important insights into therapeutic targets for cancer treatment.
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Identifying Four New Subtypes of Gastric Cancer That May Lead to New Targeted Treatments
Gastric cancer has a high mortality rate, but current classification systems haven’t been effective in helping to identify subtypes relevant for treatment of the disease.
TCGA researchers have integrated molecular data from 295 stomach tumors and have discovered four subtypes of gastric cancer.
Stratification of patients into these four subtypes paves the way for the development of new personalized therapies. -
Blood Test Helps Identify Benign Lung Nodules
When it comes to determining whether lung nodules are benign, a patient typically faces surgery and a biopsy. It’s an invasive and costly response, and, in 80 percent of cases, unnecessary. But a new study published today in Science Translational Medicine suggests that a blood test could save countless patients from the trauma of surgery. The report discusses a 13-blood-biomarker panel that may help identify lung nodules that are benign.
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New Principle of Chemo-Resistance Sheds Light on Evasiveness of Cancer Cells
Each year more than half a million people in the U.S. die of cancer – the major disease group that has seen the least improvement in cure rate in the past decades. Why is cancer so difficult to treat and why do almost all treatments, however new and sophisticated, almost inevitably fail after an initial success in shrinking the primary tumor?
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ISB Analysis May Lead to Earlier Diagnoses of Deadly Brain Tumor
ISB researchers present a computational analysis of astrocytoma tumors — including the most aggressive form called glioblastoma multiforme or GBM — that could enable better tumor characterization and classification. Having these data may lead to earlier diagnoses, which are crucial to enable more effective therapy choices for battling these tumors.
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Largest Genetics Catalog of Deadliest Brain Tumor Released
Glioblastoma multiforme (GBM) is the most common and deadliest of malignant primary brain tumors in adults. Because of its lethality, GBM was selected as the first brain tumor to be sequenced as part of The Cancer Genome Atlas (TCGA), a comprehensive project funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to map the genomes of more than 25 types of cancer. Institute for Systems Biology (ISB) is among seven data analysis centers participating in TCGA.
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Non-Darwinian Dynamics in Therapy-Induced Cancer Drug Resistance
The development of drug resistance, the prime cause of failure in cancer therapy, is commonly explained by the selection of resistant mutant cancer cells. However, dynamic non-genetic heterogeneity of clonal cell populations continuously produces metastable phenotypic variants (persisters), some of which represent stem-like states that confer resistance.
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Pan-Cancer Project
The Cancer Genome Atlas research network has launched the Pan-Cancer project to analyze multiple tumor types together to find common events across different tumors. The availability of large cohorts and multiple different types of data at the DNA, RNA, and protein levels has made the Pan-Cancer project possible.
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Unlocking Molecular Signatures of Endometrial Cancer Subtypes
Endometrial cancers affect many women in the United States. In 2012, 47,000 new cases and 8,000 deaths were estimated – making endometrial cancer the fourth most common type of cancer among US women. Accurate diagnosis of endometrial tumors is critical for doctors to determine the best treatment regimen. It turns out, however, that there are major differences between endometrial cancers — differences lurking at the molecular level. Researchers at ISB in collaboration with scientists at MD Anderson and the NIH-sponsored The Cancer Genome Atlas (TCGA) recently unlocked some of these molecular signatures, potentially allowing doctors to better distinguish aggressive cases from those that are more benign.
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Biggest Family Tree of Human Cells May Help Develop Cell-Replacement Therapies
Scientists at Institute for Systems Biology (ISB), University of Luxembourg, and Tampere University of Technology have created a method that identifies the genetic toggle switches that determine a cell’s developmental fate. This research, published on April 21 in the journal Nature Methods, may lead to new discoveries in disease treatments and tissue-regeneration technologies.
“In this elegant work, the authors propose a new way to identify genetic factors that influence cell fate based on the analysis of gene regulatory networks,” said Paul Brazhnik, PhD, of the National Institutes of Health’s National Institute of General Medical Sciences, which partly funded the work.