5 results about "Acquired resistance" patented technology

Combinations, compositions and uses of a cyclin dependent kinase 2 (CDK2) inhibitor INX-315, or a pharmaceutically acceptable salt thereof described herein, in combination with a CDK4 / 6 inhibitor for the treatment of disorders characterized by mutation of Kirsten rat sarcoma (KRAS), including but not limited to the treatment of tumors and cancers. In addition, the invention includes a method to delay acquired resistance to a RAS inhibitors in a KRAS mutant cancer, comprising administering the CDK2 inhibitor INX-315 optionally in combination or alternation with a KRAS inhibitor.

The disclosure relates to methods for treating cancer. More particularly, the disclosure relates to use of chimeric non-natural synthetic proteins, in combination with non-tyrosine targeting kinase inhibitors (NTKIs), in treating cancer and preventing intrinsic and / or acquired resistance to NTKIs.

The invention discloses a PD-1 / PD-L1 immunotherapy acquired drug-resistant mouse subcutaneous tumor model construction method based on in-vivo multi-dimensional immune landscape evolution, and relates to the field of animal model construction. Comprising the following steps: preparing tumor cells: resuscitating and amplifying an MC38 colonic adenocarcinoma cell strain, and preparing a single-cell suspension; establishing a basic model: inoculating the MC38 single-cell suspension under the skin of a homologous C57BL / 6 mouse, and establishing a tumor-bearing mouse model; drug resistance induction and screening: after the tumor grows to a predetermined volume, applying continuous treatment pressure of an anti-PD-1 or anti-PD-L1 antibody to the tumor-bearing mouse. Firstly, the tumor volume of mice in a treatment group is compared with the average volume of a control group at the same time point, response mice with the tumor volume obviously smaller than that of the control group are screened out, and primary drug-resistant individuals are excluded. Performing dynamic immune monitoring sampling; and processing and analyzing the sample. The preclinical model has the characteristics of repeatability and dynamic monitoring, and overcomes the defects of the existing preclinical model.

Provided is a novel method for treating CRPC, particularly, CRPC which has acquired resistance to an antiandrogen agent. The present invention relates to an antitumor agent wherein 3-ethyl-4-{4-[4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]-3-(propan-2-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl}benzamide or a salt thereof and an antiandrogen agent are administered in combination.

The present invention relates to the use of a pyrido[3,4-d]pyrimidin-8-one derivative in preventing, ameliorating or treating lung cancer. Specifically, the present invention is not limited to a specific KRAS mutation (G12C), and exhibited potent cell proliferation inhibitory activity at nM levels in a wide range of RAS / RAF-driven tumor cell lines, such as KRAS G12V, G12S, and Q61H mutations and an NRAS Q61K mutation. Therefore, the pan-RAF inhibitory mechanism of the present invention can effectively block various RAS / RAF downstream signaling pathways, thereby providing excellent anticancer efficacy against a wide range of KRAS / NRAS mutant cancers. In addition, the present invention demonstrated superior efficacy in overcoming complex acquired resistance mechanisms that arise after treatment with a KRAS G12C inhibitor (G12Ci), in the following two aspects. Specifically, the present invention exhibited significantly superior inhibitory efficacy than existing G12C inhibitors (G12Ci) in a KRAS G12C-Y96D model including a secondary mutation at a drug-binding site. In addition, the present invention exhibited superior or similar anticancer activity as compared to G12C inhibitors (G12Ci) in signal bypass models, such as CCDC6-RET fusion. These results indicate that the simultaneous inhibitory activity of DDRs by PHI-501 neutralizes acquired resistance by blocking bypass-activated signaling pathways, thereby overcoming acquired resistance to existing G12C inhibitor (G12Ci) therapeutic agents. In addition, the present invention demonstrated the simultaneous blockade of two pathways critical to the survival of KRAS-driven cancer cells, that is, the MAPK pathway and the PI3K / AKT bypass pathway, at the molecular level. Thus, the phosphorylation of p-ERK (a marker for MAPK activity), p-AKT (a marker for PI3K / AKT activity), and pDDR1 was significantly and simultaneously reduced in both in-vitro and in-vivo models, demonstrating that the dual mechanism of action functions effect