Methods and compositions for treating and diagnosing pancreatic cancers
Inventors
Miller, George • AYKUT, Berk • Saxena, Deepak • PUSHALKAR, Smruti
Assignees
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Publication Number
US-12685743-B2
Publication Date
2026-07-21
Expiration Date
Abstract
The application relates to methods based on modulating pancreatic and/or gastrointestinal microbiota and related antifungal compositions. Specifically, the application relates to the use of microbiome for prevention, treatment and diagnosis of pancreatic cancers or tumors, such as pancreatic ductal adenocarcinoma.
Core Innovation
The invention relates to methods for treating, preventing, and diagnosing pancreatic cancer, including pancreatic ductal adenocarcinoma (PDA), by modulating the pancreatic and/or gastrointestinal mycobiome, including pancreatic microbiota and gastrointestinal (GI) microbiota. The approaches particularly inhibit growth and/or activity of fungi from the species Malassezia globosa within the pancreatic and/or gastrointestinal microbiota of a subject.
In certain embodiments, the methods further involve determining and/or requiring a functional mannose-binding lectin (MBL)-C3 convertase complement axis, including the role of MBL and C3 convertase and signaling via C3a and the C3a receptor (C3aR). The document reports a markedly increased intratumoral fungal presence in PDA and Malassezia enrichment in tumors relative to gut and normal pancreas, supporting Malassezia as a targeted mycobiome component for modulation.
The invention also includes determining the level of at least one strain of Malassezia globosa in the pancreatic and/or gastrointestinal microbiota of the subject, including comparative assessment versus a control pancreatic and/or gastrointestinal microbiota. Diagnostic use cases are described in which Malassezia levels in the subject are compared to matched controls, including a threshold criterion for Malassezia levels being at least about 1000-fold higher, and the document further notes potential complementary bacterial biomarker panels.
Claims Coverage
The partial content includes one independent claim directed to treating pancreatic ductal adenocarcinoma using an antifungal compound that inhibits Malassezia globosa growth in pancreatic and/or gastrointestinal microbiota, while determining Malassezia globosa levels in that microbiota. Dependent claims refine the subject and assessment framework and specify additional constraints on administration and dosage.
Antifungal Malassezia-targeted treatment of pancreatic ductal adenocarcinoma
Administering to a subject in need thereof an effective amount of an antifungal compound or composition that inhibits growth of one or more strains of fungi from Malassezia globosa in the pancreatic and/or gastrointestinal microbiota of the subject, thereby treating pancreatic ductal adenocarcinoma.
Determining Malassezia globosa level in pancreatic and/or gastrointestinal microbiota
Further comprising determining the level of at least one strain of Malassezia globosa in the pancreatic and/or gastrointestinal microbiota of the subject as part of the method.
Amphotericin B or fluconazole composition limitation
Wherein the antifungal compound or composition comprises amphotericin B or fluconazole.
Control-based comparison of Malassezia globosa levels
Comparing the level of at least one strain of Malassezia globosa in the pancreatic and/or gastrointestinal microbiota of the subject to the level of the same fungi in a control pancreatic and/or gastrointestinal microbiota.
Functional MBL-C3 convertase complement axis subject feature
Wherein the subject includes a functional mannose-binding lectin (MBL)-C3 convertase complement axis.
Across the independent claim and the identified dependent refinements, the central inventive coverage is a treatment method for PDA that administers an antifungal to inhibit Malassezia globosa growth in pancreatic and/or GI microbiota, coupled with determining Malassezia globosa levels and, in refinements, using control comparisons and/or requiring a functional MBL-C3 convertase complement axis.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating pancreatic ductal adenocarcinoma by administering an antifungal compound that inhibits growth of Malassezia globosa strains in the pancreatic and/or gastrointestinal microbiota while determining Malassezia globosa levels.
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