Methods relating to lung cancer
Inventors
Pavel, Ana Brandusa • Campbell, Joshua David • Lenburg, Marc Elliott • Spira, Avrum Elliot
Assignees
Publication Number
US-12329771-B2
Publication Date
2025-06-17
Expiration Date
2038-01-23
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Abstract
The methods and assays described herein relate to detection, diagnosis, and treatment of lung cancer, e.g., by detecting the level of expression of certain miRNAs described herein and/or by therapeutically increasing the level of those miRNAs.
Core Innovation
The invention provides methods and assays related to the detection, diagnosis, and treatment of lung cancer by measuring the expression levels of certain microRNAs (miRNAs) that are under-expressed in lung cancer. By analyzing lung tissues and samples from lung cancer patients, it was discovered that specific miRNAs are decreased in expression compared to non-cancerous tissue, and that these miRNAs can act as tumor suppressors.
This technology introduces novel approaches to both the assessment and therapeutic intervention in lung cancer. Diagnostic methods include detecting and measuring the levels of at least one miRNA—selected from a defined group including miR-146a-5p, miR-324-5p, miR-223-3p, miR-223-5p, miR-450b-5p, miR-221-3p, miR-505-3p, and miR-582-5p, as well as additional miRNAs identified in Table 10 and Table 11—within samples such as bronchial brushing or nasal epithelial cells obtained from subjects.
Therapeutic methods involve administering an agonist of at least one of the under-expressed miRNAs or an inhibitor of miRNAs that are upregulated in lung cancer, as specified in Table 11. This includes the option to deliver these agents using vectors encoding relevant nucleic acids. The aim is to therapeutically increase the levels of the identified tumor suppressor miRNAs or decrease the levels of upregulated miRNAs, positively impacting lung cancer treatment.
The background clarifies that lung cancer's high mortality rate stems from inadequate detection at early stages. The problem being addressed is the need for improved diagnostics and therapeutics for lung cancer, achieved through the novel use of cancer-associated miRNA expression profiles for both early detection and treatment.
Claims Coverage
The patent includes one independent claim encompassing two major inventive features in the treatment of lung cancer.
Administration of a miRNA agonist or inhibitor for lung cancer treatment
A method of treating lung cancer in a subject in need thereof, comprising: - Administering to the subject either: - an agonist of at least one miRNA selected from the group consisting of miR-324-5p, miR-769-3p, miR-618, miR-338-5p, miR-210, miR-450a-5p, miR-30b-5p, miR-450a-5p, miR-652-3p, miR-107, miR-887, miR-147b, miR-31-5p, miR-29c-5p, miR-324-3p, miR-345-5p, miR-450b-5p, miR-769-5p, miR-326, miR-940, miR-582-5p, miR-31-3p, miR-378i, miR-505-3p, miR-1249, miR-1260b, miR-3200-3p, miR-425-3p, miR-4791, miR-1296, and miR-4677-3p; - or an inhibitor of at least one miRNA selected from the group consisting of miR-375, miR-24-1-5p, miR-130b-5p, miR-183-5p, and miR-203a. - In some embodiments, the agonist can be administered as a vector comprising a nucleic acid encoding the agonist or inhibitor.
In summary, the patent broadly covers therapeutic methods for treating lung cancer by modulating the expression of specific miRNAs through administration of agonists or inhibitors, with embodiments including the use of genetic vectors.
Stated Advantages
Described methods represent a less invasive test compared to biopsy or surgery, since they utilize bronchial brushings or nasal epithelial samples.
The technology is relatively inexpensive compared to CT screening, biopsy, or surgery.
Incorporating miRNA expression data (such as miR-146a-5p) improves the performance of existing bronchial gene expression biomarkers for lung cancer detection.
MicroRNAs are more stable and easier to measure in degraded tissues than mRNAs.
The methods allow for early detection of lung cancer by capturing gene expression changes in cytologically normal airway epithelial cells.
The test can be further simplified by moving the analysis to nose tissue, making it even less invasive.
The integrated biomarker approach can enhance the robustness and performance of lung cancer classifiers.
Documented Applications
Detection and diagnosis of lung cancer using the measurement of miRNA expression levels in bronchial brushing or nose epithelial samples.
Treatment of lung cancer by administering agonists of under-expressed miRNAs or inhibitors of upregulated miRNAs as specified.
Improvement of the diagnostic performance of existing bronchial gene expression biomarkers (such as Percepta) by addition of miRNA expression data.
Use in current or former smokers, or subjects at risk of developing lung cancer, undergoing bronchoscopy for suspected disease.
Development of less invasive clinical tests for lung cancer detection, including potential adaptation to nasal tissue sampling.
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