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Establishment of a minimally invasive protocol for early detection of malignant carcinoma in RDEB

Project lead Associate Prof Albert S Mellick
Organisation Ingham Institute for Applied Medical Research, University of New South Wales, AUSTRALIA
Partner organizations & collaborators EB House Austria
Project budget AUD 40,000
Start date / Duration 01. Mar 2019 / 22 months
Funder(s) / Co-Funder(s) Others, DEBRA Australia
Other funder(s) NHMRC- Ingham Institute Research Incentive Fund
Research area Skin cancer & fibrosis

Project details

Short lay summary

Squamous cell carcinoma (SCC) is the second most common form of skin cancer, and the most common form of nonmelanoma skin cancer. When caught early, most SCCs are curable. However, certain sub-types, such as those derived from patients with recessive dystrophic epidermolysis (RDEB), are more difficult to treat. In addition to being difficult to diagnose, SCCs from RDEB patients tend to be significantly more aggressive than SCCs identified in an otherwise healthy population. Because most cancers are treatable, if detected early there is a great need to shorten the time between diagnosis and treatment. However, current methods, which involve skin biopsies, do not encourage regular screening. Consequently, our laboratory is determined to develop less traumatic methods for diagnosing malignant RDEB SCCs.

Scientific summary

Several methods have been developed to analyse the presence of tumor cells in the blood of patients suspected of having malignant carcinoma, or one that has spread. The most notable of these protocols is the CellSearch® methodology, which utilises markers to extract and identify tumor cells that may be circulating in the blood of patients (aka circulating tumor cells or CTCs). However, because of the differential expression of some of the markers used for CTC analysis (e.g. cytokeratin), CTC analysis as a diagnostic tool when applied to EB is problematic. In previous work funded by DEBRA Australia and EB Austria we have determined that small RNAs can be diagnostic of malignancy in EB tissues. Given that we also have expertise in the identification of CTCs as early markers of malignancy we have sought to identify blood based small RNA linked CTC markers in EB patients.  A lead candidate, miR-10b, has recently been identified as expressed in malignant SCCs from EB patients (Wimmer et al. Cell Commun Signal. 2020 Apr 10;18(1):61). We have now also shown that miR-10b+ tumor cells can be identified in the blood using a filtration-based (size-exclusion) protocol (ScreenCell®), and a unique immunohistochemical technique that allows cell specific localization of small RNAs.

Strategic relevance

By the time RDEB SCCs are diagnosed they have often already spread and are difficult to treat. Consequently, there is a need for more efficient diagnostic methods. The liquid biopsy holds significant potential because it allows identification of cancer cells in the blood. Unfortunately, current liquid biopsy-based analysis developed for epithelial cancers may not be appropriate for RDEB-SCCs. By adapting filtration-based methods and using more effective markers of malignancy, such as miR-10b, we hope to provide a tool that can be used for effective screening of disseminated disease in RDEB.



Small RNAs
EB House Austria
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