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Oncology Diagnostic Technologies at the
University of Chicago
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Gene signatures and biomarkers
Glucocorticoid and androgen receptor test to
predict response to HSP90 inhibitors
Four-gene signature for assaying utility of
breast and lung cancer treatments
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Dr. Philip Connell has identified four genes involved in
DNA repair – Rif1, PARI, RAD51, and Ku80 – for which
expression level indicates prognosis and response to a
variety of therapies in breast or lunch cancer. These
expression of these four genes can be quantified to yield a
Recombination Proficiency Score (RPS).
Low RPS patients have a poor prognosis that can be
counteracted by adjuvant chemotherapy; high RPS
patients, who have a good prognosis, do not benefit from
chemotherapy
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Seven-gene signature for treatment
response in breast cancer
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Dr. Ralph Weichselbaum’s team has performed
retrospective studies to demonstrate the ability of seven
genes -- IFIT3, STAT1, IFIT1, OAS1, IF144, MX1, and G1P2 –
to identify which patients are likely to respond to adjuvant
chemotherapy or radiation. The signature has been
termed the Interferon-Related DNA-damage-resistance
Signature (IRDS).
The assay can be performed on formalin-fixed paraffinembedded tumor samples.
Several commercially-available genetic tests provide
prognostic information about the risk of recurrence for
given tumor types. However, they are not designed to
predict individual patient outcomes in response to specific
courses of treatment, for which IRDS is the only true
predictive test.
Dr. Suzanne Conzen has documented differential tumor
expression of the glucocorticoid and androgen receptors in
breast cancer cells.
Data to date demonstrates that the levels of glucocorticoid and
androgen receptor expression in tumor cell lines predict
responsiveness to HSP90 inhibitors
The technology provides a method to identify patients that will
benefit from newly emerging therapies that inhibit HSP90.
Tumor gene signature to identify immune
responsive and non-responsive tumors
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Dr. Thomas Gajewski has identified an EGR2-based gene
signature that differentiates between immune responsive and
non-responsive tumors.
Validated studies comparing gene expression profiling have
identified a key set of genes involved in the immune response to
cancer.
This diagnostic would be useful for identification of patients in
need of immune-stimulating therapy for successful treatment of
cancers.
Gene signatures and biomarkers, cont’d
DNA hypermethylation prognostic fourgene breast cancer signature
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A 4-gene expression signature of DNA hypermethylation
in breast cancer tumors is (i) prognostic of 7-year
metastasis-free survival (p=0.005); and (2) predictive of
response to DNA methyltransferase (DNMT) inhibitors.
The signature is independent of cancer subtype.
Data indicate that 10% of breast cancer patients have
high oncogene HMGA2 expression and low tumor
suppressor TET1 and HOXA7/HOXA7 expression, with a
60% 7-year survival (poor prognosis). This subset of
patients may benefit from treatment with a DNMT
inhibitor.
A distinct 10% of breast cancer patients have low
oncogene activity, high tumor suppressor activity, and a
90% 7-year survival (good prognosis).
Tumor-stroma prognostic signature for
triple-negative breast cancer
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A 4-component gene expression signature using
genes from both tumor and stroma is prognostic for
metastasis-free survival in triple negative breast
cancer patients.
The signature highlights the importance of tumorstromal crosstalk in the progression of triple-negative
breast cancers.
Several of the genes in the signature are potential
therapeutic targets in the early stages of testing.
Prognostic signature for triple-negative breast
cancer metastasis
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A novel prognostic thirty-gene DNA expression signature
(BACH1 Pathway Metastasis Signature, BPMS) identifies
patients with the most lethal metastatic forms of triplenegative breast cancer, a disease which requires aggressive
and innovative treatment.
The prognostic power of the thirty-gene signature was
validated in a retrospective study of 3600 human breast
cancer patients.
Signature complements information provided by the
Mammaprint, OncotypeDX, PAM50, and four other breast
cancer prognostic multi-gene expression signatures. Provides
prognosis for patients with more advanced or difficult-totreat cancers, and identifies the most at-risk subgroup for the
development of targeted therapies
Molecular diagnostic imaging technologies
Prolactin receptor-mediated imaging of
ovarian cancer
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Ovarian cancer is largely asymptomatic, and patients are often
diagnosed at a late stage of disease with metastases to the
omentum and peritoneum. Effective diagnosis and imaging of
ovarian cancer is critical for treating ovarian cancer.
Prolactin receptor is highly expressed on ovarian cancer cells
and labeling of the prolactin receptor ligand human placental
lactogen (hPL) can be used as a tool to image ovarian cancer.
Drs. Ernst Lengyel and Joseph Picirilli have developed a method
to utilize hPL as an MRI contrast agent for ovarian cancer
imaging. Pre-clinical tests have shown significant advantages
over existing MRI contrast agents.
Molecular diagnostic platform technologies
Affinity clamps: Engineered affinity reagents
for detection of peptide motifs
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Dr. Shohei Koide has identified a novel protein engineering
platform based directed domain-interface evolution for
developing renewable, high affinity and high specificity
antibody-like proteins to diverse and difficult targets, such as
post-translational modifications.
The level of affinity and the mode of target recognition of
affinity clamps parallel peptide–major histocompatibility
complex interactions. Because of the simple and modular
architecture, affinity clamps are particularly well suited as
building blocks for designing more complex functionalities, such
as biosensors.
Dr. Koide has developed affinity clamps against protein-specific
phospho-tyrosines that may be used for the diagnosis of chronic
myelogenous leukemia and Noonan syndrome.
First-in-Class recombinant antibodies for the
enablement of chromatin-based diagnostics
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High-quality, reliable antibodies are needed for chromatinbased diagnostics.
Investigators have made technological breakthroughs that
enable the creation of high-quality recombinant antibodies to
histone post-translational modifications. A series of
recombinant antibodies have been generated against trimethylated residues on histones 3 and 4 that may be useful for
the diagnosis of facioscapulohumeral muscular dystrophy,
breast cancer, and renal cell carcinoma.
Clinical studies for the diagnosis of facioscapulohumeral
muscular dystrophy are underway.
Diagnostic imaging technologies
Better Image Reconstruction with Less
Patient X-Ray Dose
3D Imaging for Histology
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Dr. Patrick La Riviere has developed x-ray visible stains and
computational imaging tools that combines the key benefits of 3D
X-ray imaging with histology.
Markets include: pathology examination of surgical samples and
research tool applications.
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Dr. Xiaochuan Pan has developed advanced 3D reconstruction
algorithms for x-ray based imaging.
Enables new imaging modalities. E.g. in surgical suite, dental
office.
Can reduce patient times in CT machines and reduce X-ray dose
to patients.
Available Diagnostic Technologies
Oncology Diagnostics: Gene signatures and Biomarkers
UCHI 2228
(Rosner)
Prognostic gene signature for survival of triple negative breast cancer
UCHI 2232
(Gajewski)
An EGR2-based gene signature for the identification of patients who
would benefit from immune-stimulating anti-cancer therapy
UCHI 1374
A genetic signature which correlates with the response of breast
cancer patients to both radiotherapy and chemotherapy
Initial retrospective studies have confirmed the signature, a larger scale
analysis is planned
UCHI 2280
(Conzen)
Glucocorticoid and androgen receptor expression as predictive assay
for breast cancer patient response to treatment with Hsp90 inhibitors
Data in triple negative breast cancer cell lines ; follow-up studies are
ongoing
UCHI 2273
(Connell)
Four-gene prognostic and predictive signature for breast/lung cancer
Predicts response to adjuvant chemotherapy and DNA damaging
therapies
UCHI 2241
(Rosner)
Prognostic four-gene breast cancer signature for metastasis-free
survival
Predicts response to DNMT inhibitors
UCHI 2383
(Rosner)
Tumor-stroma prognostic signature for triple-negative breast cancer
Prognostic for metastasis-free survival in triple negative breast cancer
patients
(Weichselbaum)
Further stratification of patients identified as having a poor prognosis by
the Mammaprint and Oncotype clinical tests
Validated preclinical studies comparing gene expression profiling have
identified a key set of genes involved in the immune response to cancer,
and additional in vivo confirmation is ongoing
Available Diagnostics Technologies
Molecular Diagnostic Imaging Technologies
UCHI 1418
(Lengyel)
Labeled prolactin as an MRI contrast agent for ovarian cancer imaging
Pre-clinical tests have shown significant advantages over existing
MRI contrast agents
Molecular Diagnostic Platform Technologies
UCHI 2225
(Koide)
Affinity clamps for peptide motifs
UCHI 2089 (Koide) Recombinant antibodies
High affinity and high specificity antibody-like proteins to diverse
and difficult targets
First-in-class molecules, identify post-translational modifications
Diagnostic Imaging Technologies
UCHI 2088 (La
Riviere)
UCHI 1343 (Pan)
3D imaging for histology
Combines the key benefits of 3D X-ray imaging with histology
Image reconstruction with lower x-ray dose
Reduces patient time in CT machines, allows for lower x-ray
dose
How to Partner with the University of Chicago
Contact UChicagoTech, the Center for Technology Development & Ventures,
to learn more.
We build strong industry partnerships to successfully bring innovation to the
marketplace. UChicagoTech can connect you to emerging technologies and fieldadvancing researchers that may inform and enrich your own innovation efforts. We
value your involvement at every stage of the invention pipeline, from idea to tangible
asset. For more information, visit us at tech.uchicago.edu or contact anyone on the
Oncology team.
Steven Kuemmerle, PhD
Deputy Director
Phone: 773-834-3211
[email protected]
Divya Varshney, MBA
Chief Marketing Officer
Phone: 773-702-8696
[email protected]
Margaret Fleetwood, PhD
Project Manager
Phone: 773-834-4619
[email protected]