Synthetic lethality and the treatment of cancer
Inventors
Berthiaume, Luc G. • Beauchamp, Erwan • Perinpanayagam, Conganige Maneka Anne • Yap, Chuiyee
Assignees
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Publication Number
US-12343341-B2
Publication Date
2025-07-01
Expiration Date
Abstract
Described herein are compounds, compositions and methods for treatment of cancer. Also described are methods and uses for identifying subject with cancer that are suitable for treatment with the compounds, composition and methods are described herein. In one aspect of the present invention, there is provided a method of treating a subject having a cancer deficient in NMT2, comprising: administering to said subject an NMT inhibitor.
Core Innovation
The patent describes synthetic-lethality-based cancer therapy that targets N-myristoyltransferases, in particular by treating a cancer in a human subject using an inhibitor of NMT1 protein. The approach includes identifying a human subject as suitable for NMT1 inhibition by assessing NMT1 and NMT2 protein levels in a sample containing cancer cells, with suitability determined by NMT1 protein being present and NMT2 protein level being low or absent compared to an NMT2 protein level present in a normal human B-Cell.
In the disclosed patient-selection framework, NMT1 protein level and NMT2 protein level are measured using devices configured to measure the respective proteins. The comparison reference is a normal human B-Cell for NMT2 protein level. The patient-selection determination that NMT1 is present and NMT2 is low or absent is used to identify the human subject as suitable for treatment.
The treatment includes administering an NMT1 inhibitor, where the NMT1 inhibitor is DDD85646 or a derivative thereof, as part of the method of treating the cancer. The document further describes that the therapy is directed to cancers deficient in NMT2, including B-cell lymphomas, and includes the concept of combining NMT1 inhibition with a chemotherapeutic agent and selecting lymphoma subtypes within the disclosed B-cell lymphoma set.
Claims Coverage
The independent claim covers a subject-selection method with two protein measurements followed by administering an NMT1 inhibitor. Dependent claims narrow the cancer or lymphoma type and optionally add a chemotherapeutic agent.
Patient suitability based on NMT1 presence and NMT2 low or absent status
A method of treating a cancer in a human subject by identifying the human subject as suitable for treatment with an inhibitor of NMT1 protein by measuring NMT1 protein level and measuring NMT2 protein level in a sample containing cancer cells, and determining from the measured NMT1 and NMT2 protein levels that NMT1 protein is present and that the NMT2 protein level is low or absent as compared to an NMT2 protein level present in a normal human B-Cell.
DDD85646 administration after NMT1 and NMT2-based identification
Administering the inhibitor of NMT1 to the human subject, wherein the NMT1 inhibitor is DDD85646, or a derivative thereof.
Treatment of lymphoma restricted to specified B-cell lymphoma subtypes
The method is characterized such that the cancer is a B cell lymphoma, and the B cell lymphoma is one of follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, B-CLL/SLL, immunocytoma/Waldenstrom's, MALT-type/monocytoid B cell lymphoma, Burkitt's lymphoma, a pediatric lymphoma, or anaplastic large cell lymphoma.
Combination with chemotherapeutic agent selected from an enumerated regimen list
A method further comprises administering a chemotherapeutic agent, wherein the chemotherapeutic agent is one of CHOP, GAP-BOP, m-BACOD, ProMACE-MOPP, ProMACE-CytaBOM, MACOP-B, IMVP-16, MIME, DHAP, ESHAP, CEFF (B), CAMP, VABCD, ABDIC, CBVD, PCVP, CEP, EVA, MOPLACE, MINE, MTX-CHOP, CEM, CEVD, CAVP, EVAP, or EPOCH.
Across the independent claim and its dependents, the inventive coverage centers on identifying suitability for NMT1 inhibition using measured NMT1 and NMT2 protein levels with a normal human B-Cell comparison reference, administering DDD85646 or a derivative, optionally narrowing to specified B-cell lymphoma subtypes, and optionally combining with a chemotherapeutic agent chosen from an enumerated regimen list.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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