10 results about "Acquired resistance" patented technology

Targeted therapy using osimertinib (an EGFR tyrosine kinase inhibitor), is the first choice for patients with metastatic or recurring lung cancer. However, most patients develop resistance. Because the options after failure of TKls such as osimertinib are limited, improving EGFR-targeted therapy is an unmet need. Here, EGFR mutant patient-derived xenograft tumors responded partially to osimertinib despite near complete inhibition of EGFR activation. Many tumor cells escaped drug killing and regained growth following about 35 days of continuous osimertinib dosing. However, when an antibody to hepatoma-derived growth factor was given concurrently with osimertinib, tumors showed complete or near complete responses with significant prolongation of progressionfree survival of tumor bearing mice. The data support the idea that increased suppression of the AKT / mTOR and MAPK pathways is a mechanism that enhances efficacy of osimertinib when it is combined with an anti-HDGF antibody.

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 are: a novel therapeutic agent for fungal infections caused by Candida auris or Cryptococcus neoformans, which have acquired resistance to an azole-based antifungal agent; and a method for identifying resistant fungal strains, the method being performed prior to treatment with said therapeutic agent.　The therapeutic agent is characterized by combining an azole-based antifungal agent and milbemycin as active ingredients. The identifying method is characterized by using an azole-based antifungal agent-added and milbemycin-added fungal isolation medium and an azole-based antifungal agent-added and milbemycin-free fungal isolation medium.

The invention relates to the technical field of molecular oncology and drug resistance mechanism research, and discloses an S232F site of acquired drug resistance of a fusion gene STRN3-RARA and application of the S232F site in ATRA. The product is used for detecting the sensitivity of a patient suffering from acute promyelocytic leukemia to all-transretinoic acid (ATRA) treatment or screening whether the patient suffering from acute promyelocytic leukemia is resistant to ATRA treatment, an S232F mutation site is an STRN3-RARA fusion gene coding protein region mutation site, and the nucleotide sequence of the STRN3-RARA fusion gene is shown as SEQ ID NO: 1. The S232F mutation site is located at the 974th nucleotide site of the nucleotide sequence, and the base C is mutated into T. According to the present invention, the S232F mutation site can be adopted as the drug resistance detection marker, the reagent or the kit can be designed according to the STRN3-RARA gene S232F mutation site so as to be used for clinical drug resistance detection, and the gene mutation state of the patient can be monitored so as to guide the personalized drug use.

The present disclosure relates to methods for the treatment of diseases or disorders (e.g., cancer) with mTOR inhibitors. Specifically, the disclosure relates to methods of treating a subject having a cancer by administering a particular dosage of an mTOR inhibitor. In some embodiments this disclosure includes methods for delaying, preventing, or treating acquired resistance to RAS inhibitors using a dosage of an mTOR inhibitor. In some embodiments, this disclosure relates to methods of treating or preventing adverse events associated with administration of an mTOR inhibitor using tacrolimus.

A bispecific antibody targeting EGFR and c-Met. By means of modifying the amino acid sequence of an Fc segment of a binding arm, the heterodimeric interaction between an EGFR binding arm and a c-Met binding arm of the bispecific antibody is stronger than the interaction of the respective homodimers, such that a heterodimer can be assembled in vitro. The bispecific antibody is more effective in inhibiting the proliferation of EGFR and c-Met double positive tumor cells than a combination of an EGFR monoclonal antibody and a c-Met monoclonal antibody. The bispecific antibody mediates antibody-dependent cytotoxicity (ADCC), promotes target protein internalization, and inhibits the cell proliferation of the strain with acquired resistance to osimertinib. The prepared bispecific antibody is simple to prepare and stable in structure, a pure bispecific antibody is obtained by means of in-vitro assembly, and the bispecific antibody is expected to better meet clinical treatment needs, and therefore the bispecific antibody has good market prospects.

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