Combination treatment of cancer

Inventors

Brünner, Nils Aage • Christophersen, Palle • Stenvang, Jan • Lichtenberg, Jens • Thougaard, Annemette

Assignees

Scandion Oncology AS

Abstract

The present invention relates to treatment of cancer, in particular to methods of sensitising cancer cells to an anti-cancer therapy by administering an effective amount of a modulator of Volume Regulated Anion Channels, i.e. a VRAC modulator.

Core Innovation

The patent describes a cancer treatment regimen based on administering an effective amount of a Volume Regulated Anion Channel (VRAC) modulator to a subject. In particular, the VRAC modulator is defined as a compound of general formula I or a pharmaceutically acceptable salt thereof, where R2 represents tetrazolyl and multiple other substituents are independently selected from groups such as hydrogen, halo, trifluoromethyl, nitro, alkyl, alkylcarbonyl, and various aryl or heteroaryl substituents.

The problem addressed is the treatment of cancer that is resistant to an anti-cancer agent, including de novo or acquired chemoresistance. The document connects VRAC with cell volume regulation, including regulatory volume decrease, and drug-related processes, and frames the treatment approach as sensitizing, potentiating, or re-sensitizing cancer cells to anti-cancer therapies using VRAC inhibition.

The disclosed approach includes using VRAC blockers, with representative examples discussed such as NS3728 (Endovion; SCO-101) and related compounds, together with an effective amount of an anti-cancer agent. The document reports enhanced or additive and/or synergistic effects when NS3728 is combined with multiple anti-cancer agents across drug-resistant settings, including glioblastoma, colorectal cancer, and breast cancer, and it further includes anti-estrogens such as tamoxifen and fulvestrant.

Claims Coverage

The independent claims cover methods of treating cancer by administering an effective amount of a VRAC modulator defined by general formula I, or a pharmaceutically acceptable salt, together with an effective amount of an anti-cancer agent, for cancers resistant to the anti-cancer agent. The inventive features center on the VRAC modulator structural definition and the cancer patient selection criteria, including resistance and, in some claims, solid tumor and metastatic cancer.

Across the independent claims, the core claim coverage is a cancer treatment method that administers a VRAC modulator defined by general formula I together with an effective amount of an anti-cancer agent, where the cancer is resistant to the anti-cancer agent. The claim context further narrows the indication to solid tumors and metastatic cancer.

Stated Advantages

Documented Applications