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Tag: Showe

(left) Dr. Louise Showe works with a young scientist in the lab. (right) Dr. Andrew Kossenkov

Powering Cancer Research

Written by The Wistar Institute on . Posted in Featured News.

Wistar’s scientific accomplishments could not be achieved without the support of our donors who recognize our research strengths, share our vision and are committed to tackling disease, improving human health and answering the most pressing scientific questions.

Dr. Jerry Francesco’s support is behind the latest developments in the cancer research of Dr. Louise Showe, professor in the Molecular & Cellular Oncogenesis Program of The Wistar Institute Cancer Center.

Dr. Showe is helping advance the development of a blood-based test to detect cancer at an early stage in nonsmokers with no family history of lung cancer as well as people with an increased risk, as early detection makes a difference for this most hard-to-treat cancer. Dr. Francesco learned about Dr. Showe’s work in 2019, and since then has been an essential part of making a lung cancer early diagnosis test a reality.

“The potential of this project to develop a clinical, non-invasive test based on blood gene expression is incredible,” said Showe. “There are a number of possibilities for the project including using this test to diagnose lung cancer in at-risk populations. It could also be used as a follow up test after treatment to monitor cancer recurrence. And further along in development, it could even be a test for screening the general population to help in early detection.”

Dr. Showe collaborates closely with Dr. Andrew Kossenkov, assistant professor in the Vaccine & Immunotherapy Center and member of the Gene Expression & Regulation Program. In 2007, Dr. Kossenkov started as a postdoctoral fellow in the Showe lab where the lung cancer diagnostic project quickly became his main focus for years to come. Dr. Kossenkov is now the scientific director of the Bioinformatics Facility.

“This is a very exciting project of great proportion and importance with the final goal of making a non-invasive lung cancer diagnosis from blood,” said Kossenkov. “Besides great clinical down-the-road impact, it was a technically and logistically complex endeavor, and we had to go through multiple iterations and approaches during the span of the project. That was and continues to be an exciting time and helped me to increase my expertise in the field tremendously.”

Because of donors like Dr. Francesco, Wistar scientists see the fruits of their research move forward in directions that are visionary and out of the box. Philanthropic support also gives researchers a leg up to gather the data needed to apply for large federal grants.

Wistar’s Science Discovery Fund connects philanthropists and scientists together to solve some of the biggest issues in cancer and infectious disease. It is the vehicle through which the donor community can learn about and support the highest-risk, potentially high-reward research taking place. Side by side with researchers, they move discoveries into future diagnostics or drug targets that help scientists translate basic discoveries into next-generation vaccines and medicines.

We spoke to Dr. Francesco about Dr. Showe’s work and his contributions that helped her advance a lung cancer diagnostic for one of the most common causes of cancer deaths in men and women worldwide,1 accounting for 2.1 million new cases and 1.8 million deaths in 2018.2 Twenty percent of those U.S. deaths were nonsmokers who may have smoked less than 100 cigarettes in their lifetime or might have been genetically predisposed or driven by a molecular abnormality or change.

Dr. Francesco wants people to know that Wistar scientists are a highly committed team that possesses a broad range of scientific interests and cutting-edge expertise, with an aim toward practical solutions to disease.

“I think Wistar research is the finest in the country, if not the world,” said Dr. Francesco. “Dr. Showe’s research is of immense interest because of the sad state of affairs in early diagnosis of lung cancer and for the hope of developing simple and readily available tests for this terrible disease. I only wish such tests were available for my beloved wife Lucille who passed from lung cancer. I hope that my philanthropy will help speed the early diagnosis of lung cancer so that eventually such tests can be used by family physicians in their practice. I am happy to play a small role in this project.”

Sources:

1 World Health Organization Cancer Fact Sheet, 2018
2 Source: Yale Medicine;

Finding Cancer Early to Save Lives

Written by The Wistar Institute on . Posted in Featured News.

Early diagnosis and screening are the bedrock for addressing cancer in a timely fashion to improve patient survival, yet laboratory diagnostics are lagging behind and so far, are limited to a few specific biomarkers for several malignancies.

Wistar scientists are advancing innovative research and discovering new biomarkers that may be useful for the development of simple, highly specific and sensitive diagnostic tests that could be used to detect cancer in its early stages, when the chances of successful treatment are significantly higher.

Lung Cancer

Symptoms of lung cancer, the primary cause of cancer-related deaths worldwide, do not appear until the disease is advanced and likely untreatable, and adequate early detection methods are scarce.

In the past decade, advances in imaging technologies have reduced mortality by 20% among high-risk individuals. However, these techniques are not specific enough to distinguish between benign and malignant lung nodules, especially the smallest ones, which are particularly challenging to diagnose and not easily accessible for further analysis. As many as 96% of these nodules prove to be false positives when analyzed histologically after invasive surgical procedures.

The development of alternative non-invasive approaches to assess these difficult-to-diagnose nodules is a critical goal in pulmonary medicine. Such techniques would also be useful to identify at-risk individuals who would benefit from imaging follow up.

Research by Louise C. Showe, Ph.D., professor in the Molecular & Cellular Oncogenesis Program at Wistar, led to the identification of a panel of biomarkers circulating in the blood that could help detect lung cancer in high-risk patients using gene expression analysis. Studies so far have shown that this strategy is both highly sensitive and specific in distinguishing cancerous nodules from benign nodules.

Dr. Showe’s research program began in 2004 and was originally supported by funds from the Pennsylvania Department of Health through the tobacco settlement CURE Program. Further support was provided by OncoCyte Corp., and most recently by a multi-year grant from the Early Detection Research Network (EDRN), an initiative of the National Cancer Institute (NCI) that supports collaborative efforts to accelerate the translation of biomarker information into clinical applications. In addition, generous philanthropic partnerships have been forged via the Wistar Science Discovery Fund in support of our lung cancer biomarker development.

OncoCyte Corp. has exclusively licensed the lung cancer biomarker technology from Wistar and is working to complete clinical validation studies of the confirmatory lung cancer diagnostic test. In parallel, Dr. Showe is continuing to investigate new unique gene expression signatures that may be useful in the diagnosis and prognosis of lung cancer.

Glioblastoma

The Showe lab is also working on creating a molecular test for the subtyping and stratification of patients diagnosed with glioblastoma, the most common and deadly type of primary malignant brain cancer in adults, that is in urgent need for assessing the response to new therapy-directing tools.

There is no known cure for glioblastoma and patients often succumb to the disease within one to two years of diagnosis. Unfortunately, glioblastoma is a complex tumor type with many different subtypes that may respond differently to various forms of cancer treatment. When patients get diagnosed, there is no treatment choice. Dr. Showe and colleagues are trying to change that, recognizing that grouping patients by subtype is an important first step for clinicians to identify and for pharmaceutical companies to develop more effective treatment strategies. Wistar is among a few leading institutions that specialize in brain tumor research and are working towards this goal.

The Wistar spin-out ISOMA Therapeutics, LLC., is advancing a glioblastoma-subtyping technology based on jointly owned patent applications of Wistar and The University of Pennsylvania. The company is developing the subtyping assay as a companion diagnostic to help direct the use of personalized therapies for glioblastoma patients.

Ovarian cancer

Another critical area of unmet need for sensitive and specific diagnostic tools is in the field of ovarian cancer – the most lethal of all gynecological malignancies, for which early diagnosis makes a huge difference in terms of survival. In fact, when ovarian cancer is caught early, five-year survival is close to 90%, a percentage that plummets to less than 30% if patients are diagnosed after the cancer has spread. Unfortunately, most ovarian cancer cases are diagnosed too late, because the disease tends to be asymptomatic at earlier stages and the ovaries are difficult to access by imaging or other minimally invasive methods.

In addition to physical examination and ultrasound imaging, measurement of elevated serum levels of a cancer antigen called CA125 helps primary care physicians manage patient treatment after ovarian cancer has been diagnosed by other methods. However, there are no FDA-approved ovarian cancer diagnostic tests available to detect cancer prior to the onset of symptoms.

Wistar’s David Speicher, Ph.D., professor and co-leader of the Molecular & Cellular Oncogenesis Program, and his team have identified a group of novel biomarkers for detecting ovarian cancer, including CLIC1 and CLIC4, that are found both in cancer tissue samples and in the patients’ blood and are common to all the subtypes of ovarian cancer. His lab has shown that when ovarian cancer tissue is stained by antibodies to CLIC1 and CLIC4, they appear to be complementary to CA125. As these proteins have been detected in blood from cancer patients at higher levels than in non-cancer controls, these proteins might show improved diagnostic sensitivity and specificity compared with CA125 alone.

Dr. Speicher is interested in combining these new biomarkers with known ovarian cancer biomarkers including CA125 and HE-4, another FDA approved biomarker, to increase the breadth and depth of patient screening. Research to develop robust multi-plexed assays to support this initiative are underway in his laboratory.

All of these research efforts tell us one thing: when it comes to cancer, understanding the present helps predict the future to define the most effective course of action and improve survival.