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.
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 Discover 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.
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.
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.