Kras Inhibitor for Use in Treating Cancer

Simple SummaryContent extracted from patent full text and abstract with AI.

This patent describes the use of inhibitors targeting the native, non-mutated (wild-type) KRAS protein for the prevention and treatment of malignant melanoma and hepatocellular carcinoma. Unlike many typical cancer therapies that focus on mutated oncogenes, this approach focuses on inhibiting normal KRAS, which is shown to be upregulated and play a crucial role in cancer cell survival and drug resistance. The invention further details how combining KRAS inhibitors with other pathway inhibitors (e.g., BRAF, EGFR, CRAF inhibitors) can produce synergistic effects, overcome resistance to existing treatments, and enhance the effectiveness of therapy. The patent covers various types of KRAS inhibitors, including small molecules, siRNAs, and antibodies, and provides evidence of effectiveness both in vitro and in vivo.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment of malignant melanoma, especially cases with acquired resistance to BRAF inhibitors.
• Treatment of hepatocellular carcinoma (liver cancer), including cases resistant to standard therapies like sorafenib.
• Use as a combination therapy with existing drugs such as BRAF inhibitors (e.g., vemurafenib, dabrafenib), EGFR inhibitors (e.g., erlotinib), or CRAF inhibitors (e.g., sorafenib) to achieve synergistic anti-cancer effects.
• Prevention of the emergence of drug resistance in melanoma and liver cancer treatments.
• Potential use in immunotherapy regimens for melanoma and liver cancer as a sensitizer to immune checkpoint inhibitors.
• Development of pharmaceutical compositions containing KRAS inhibitors for administration as standard-of-care or adjunct therapies.

BenefitsContent extracted from patent full text and abstract with AI.

• Targets a novel and previously underexploited cancer pathway—wild-type KRAS—in melanoma and liver cancer, independent of known mutations.
• Overcomes the common and challenging issue of drug resistance, especially resistance to BRAF inhibitors in melanoma and sorafenib in hepatocellular carcinoma.
• Combination approaches lead to synergistic effects, meaning greater tumor cell apoptosis and reduced proliferation at lower drug doses, potentially reducing side effects.
• Shown to be effective for both primary tumor cells and metastatic cells, as well as in vitro and in vivo models, highlighting broad applicability.
• Potential to re-sensitize tumors that were previously resistant to standard therapies, improving patient outcomes.
• May reduce the emergence of further resistance compared to single-agent therapies, supporting durable responses.
• Provides a variety of inhibitor modalities (small molecules, siRNA, antibodies), giving flexibility in drug development and clinical application.
• Offers the opportunity to enhance the effectiveness of chemotherapies and immunotherapies in hard-to-treat cancers.

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Inventors & Applicants

Patent Abstract

The present invention refers to inhibitors of native, non-mutated KRAS for use in preventing and/or treating malignant melanoma and/or hepatocellular carcinoma. In addition, a KRAS inhibitor is combined with an inhibitor of another factor of the Ras-Raf- MEK-ERK pathway such as a BRAF inhibitor to reach synergistic inhibitory effects and to overcome tumor cell resistance. The invention is further directed to pharmaceutical compositions comprising such inhibitor and a pharmaceutically acceptable agent.