57 results about "Resistant cancer" patented technology

This invention discloses a butyrolactone compound with multidrug resistance reverse transcription activity, its preparation method, and its uses. The compound's structural formula is shown in Figure I. The preparation method includes the following steps: fermenting *Aspergillus pyrolyticus* (accession number CCTCC NO: M2014086) to obtain a butyrolactone fermentation product; extracting the fermentation product with ethyl acetate to obtain a crude extract; degreasing the crude extract with hexane and dichloromethane to obtain a final extract; and purifying the final extract using normal-phase silica gel column chromatography, reversed-phase medium-pressure column chromatography, and reversed-phase semi-preparative high-performance liquid chromatography. The advantage of this butyrolactone compound is that it possesses multidrug resistance reverse transcription activity and the ability to regulate P-gp-mediated drug efflux in multidrug-resistant cell lines, making it a potential drug for treating multidrug-resistant cancers.

Substituted pyrrolo[2,3-d]pyrimidines as inhibitors for multi-resistant cancers are described herein. Also provided herein are methods of forming the compounds, methods for inhibiting aurora kinase A and / or aurora kinase B activity and epidermal growth factor activity, methods of treating, ameliorating, or preventing cancer, and uses of the compounds for inhibiting aurora kinase A and / or aurora kinase B activity and epidermal growth factor receptor kinase activity. The compounds are generally of the formulas as illustrated herein, including those of Formula (I-2) or a pharmaceutically acceptable salt thereof:wherein: X1 is N; X2 is N; X3 is —NH—; X4 is N or CR2; X5 is CH, CCH3, or CCOOH; L1 is —NR4—R1; L2 is NH2 or H; R1 is:R2 is H, COOH, a 5-membered heteroaryl, or X6R3; X6R3 is as described herein; R4 is H; R5 is as described herein; and m is 1, 2, 3, 4, or 5.

The present invention represents a novel hybrid of the two natural products sclareol and doxorubicin, in the form of their conjugates. These compounds are in the form of conjugates wherein doxorubicin and sclareol are covalently linked by a linker in a molar ratio of 1: 1. The hybrid has been shown to have anti-cancer properties and is effective in the treatment of cancer cells resistant to a P-glycoprotein membrane transporter responsible for resistance to doxorubicin. Hybrid have been tested on different types of cell lines, including human glioblastoma, non-small cell lung cancer, and colorectal cancer. The invention further relates to a method for the production thereof and to the use thereof in pharmaceutical products or pharmaceutical preparations. The research results include the cytotoxic activity of single compounds, combined compounds, and conjugated compounds in sensitive and resistant cancer cell pairs with and without P-glycoprotein expression. The selectivity to cancer cells is determined by comparison with commercially available normal human lung fibroblasts. The study also studies the nanoparticle properties of the hybrids, their intracellular localization and in vivo toxicity.

The present invention relates to a composition for inhibiting multidrug resistance, the composition containing an autocrine motility factor (AMF) as an active ingredient. Specifically, treating cancer cells with an AMF protein or an AMF peptide inhibits the mRNA and protein expression of P-glycoprotein or multidrug resistance related protein-1 (MRP-1), which are major causes of multidrug resistance, and administering the AMF protein or AMF peptide in combination with an anticancer agent inhibits the release of the anticancer agent from cells, thus having the effect of increasing the accumulation of the anticancer agent inside cancer cells. Therefore, the composition can be effectively used as a pharmaceutical composition for inhibiting multidrug resistance to an anticancer agent or as an anticancer adjuvant for multidrug-resistant cancer.

To provide a therapeutic agent for PARP inhibitor-resistant cancer.SOLUTION: The present invention relates to a pharmaceutical composition for treating or preventing a solid cancer patient having resistance to a PARP inhibitor, and the pharmaceutical composition according to the present invention can effectively reduce the size of a tumor in a patient having resistance to a PARP inhibitor.SELECTED DRAWING: Figure 4

Embodiments disclosed herein use forward genetics tools (e.g., ORF libraries, perturbation libraries) to study fitness advantages under immune pressure, including resistance mechanisms. Once the resistance mechanisms are identified, vulnerabilities (i.e., dependencies) in resistant cells can be identified (e.g., synthetic lethality screens in resistant cancer cells). For example, drug or CRISPR screening can be performed in cells with an identified resistant state. Embodiments disclosed herein also provide targets for resistance to IFN-y treatment.

The present invention relates to combination therapies for treating cancer, optionally chemotherapy-resistant cancers, in a subject. The combination therapies comprise (a) an antibody or antigen-binding portion thereof that specifically binds to CD40, and (b) chemotherapy. The invention also relates to pharmaceutical compositions, kits and methods of using such therapies.

The present invention relates to a pharmaceutical composition for preventing or treating anticancer drug-resistant cancer, containing rucaparib camsylate as an active ingredient. Rucaparib camsylate can function as an immune checkpoint inhibitor by blocking the binding of PD-1 and PD-L1, and thus can be effectively used in pharmaceuticals for the prevention or treatment of cancer. In addition, rucaparib camsylate according to the present invention has an excellent anticancer effect against uterine sarcoma cancer that exhibits resistance to doxorubicin, and thus can be very effectively used for the prevention or treatment of resistant cancer.

The present invention provides, inter alia, methods, pharmaceutical compositions and kits for treating or ameliorating the effect of cancer in a subject that is refractory or resistant to non-ERK MAPK pathway inhibitor therapy. Also provided are methods for identifying subjects with cancer that would benefit from therapy with an ERK inhibitor and for inhibiting phosphorylation of RSK in cancer cells that are refractory or resistant to a non-ERK MAPK pathway inhibitor.

The present invention relates to a composition for the prevention or treatment of cisplatin-resistant cancer comprising an inhibitor of DUSP23 expression or activity as an active ingredient. It was found that DUSP23 expression is upregulated in cell clusters exhibiting characteristics of cancer stem cells, and that knocking down DUSP23 significantly reduces cell cluster formation as well as decreases the expression of SOX2, a major stem cell marker. Furthermore, DUSP23 expression was increased in lung cancer cells that had developed cisplatin resistance, and it was confirmed that the downregulation of DUSP23 inhibits self-renewal and invasive capabilities during the induction of cancer cell death. In addition, it was confirmed that DUSP23 plays an important role in promoting cancer stem cell characteristics through SOX2 expression. In conclusion, it has been shown that targeting DUSP23 can be a promising therapeutic strategy to overcome anticancer drug resistance in lung cancer, and the composition of the present invention is expected to be usefully utilized as a treatment for lung cancer cells with cisplatin resistance.

Small molecule ERα biomodulators that kill therapy-resistant ERα positive breast, ovarian, and endometrial cancer cells are disclosed. In one embodiment, the small molecule biomodulator has increased therapeutic utility because of an increased ability to kill therapy-resistant cancer cells compared to BHPI and other conventional therapies (endocrine therapies, tamoxifen, and fulvestrant / ICI). The small molecule biomodulators not only inhibit proliferation of the cancer cells but kills them, which prevents reactivation of tumors years later. Compounds of the invention, such as ErSO-TFPy, are effective for treating ERα positive cancers such as breast cancer, ovarian cancer, uterine cancer, cervical carcinoma, endometrial cancer, and the like.

The invention discloses a formamide pyrazole compound as well as a pharmaceutical composition and application thereof. The compound has a structure as shown in a formula (I), has relatively strong anti-proliferative activity on a TRK xDFG mutation drug-resistant cell strain Ba / F3-LMNA-NTRK1-G667C, can effectively down-regulate the TRKAG667C protein level in a Ba / F3-LMNA-NTRK1-G667C cell, has an application value as a TRK degradation agent, is used for preparing an anti-tumor drug, and particularly provides a new drug molecule for treating mutation drug-resistant cancers.

The invention provides compositions and methods for treating a refractory, relapsed or resistant cancer or a chronic infectious disease. In particular the present invention relates to a modified immune cell with reduced SUV39H1 activity, for use in the treatment of a patient suffering from a refractory, relapsed or resistant cancer or suffering from a chronic infectious disease, wherein the cell expresses one or more engineered antigen-specific receptors that bind an antigen associated with the cancer or the chronic infectious disease

The invention represents new hybrid compounds of two natural products sclareol and doxorubicin in the form of their conjugates. These compounds are in the form of conjugates, where doxorubicin and sclareol are covalently linked by a linker in a 1:1 molar ratio. The hybrids have shown to possess anticancer properties and are effective in treating resistant cancer cells that have P-glycoprotein membrane transporter, responsible for resistance to doxorubicin. The hybrids have been tested on different types of cell lines, including human glioblastoma, non-small cell lung carcinoma, and colorectal carcinoma. Also, a method for their preparation and their use in medical products or pharmaceutical preparations has been determined. The results of the study include the cytotoxic activity of single, combined, and conjugated compounds in pairs of sensitive and resistant cancer cells, with and without P-glycoprotein expression. The selectivity towards cancer cells was determined by comparing with commercially available normal human lung fibroblast cells. The study also investigated the nanoparticle nature of hybrid compounds, their intracellular localization and toxicity in vivo.

The present invention relates to a pharmaceutical composition for the prevention or treatment of anticancer-agent-resistant cancer, containing trovafloxacin as an active ingredient. The trovafloxacin can function as an immune checkpoint inhibitor by blocking the binding between PD-1 and PD-L1, and thus can be effectively used in medicines for the prevention or treatment of cancer. In addition, the trovafloxacin according to the present invention has an excellent anticancer effect against uterine sarcoma showing resistance to doxorubicin, and thus can be very effectively used for the prevention or treatment of resistant cancer.

The invention provides an mRNA (messenger Ribonucleic Acid) medicine for inhibiting tumor stem cells and reducing the dryness of the tumor cells and a preparation method of the mRNA medicine. The mRNA medicine comprises any one or a combination of at least two of linear PTEN mRNA, self-replicating PTEN mRNA and annular PTEN mRNA; the linear PTEN mRNA comprises a 5 'UTR (Untranslated Region) sequence, a PTEN protein coding sequence and a 3' UTR sequence; the nucleotide sequence of the PTEN protein coding sequence comprises a sequence as shown in SEQ ID NO. 1. The mRNA nano-drug prepared by the invention not only has high transfection efficiency in tumor stem cells, but also can induce differentiation of the tumor stem cells and remarkably inhibit growth of the tumor stem cells; in drug-resistant tumor cells, the stemness of the drug-resistant tumor cells is inhibited, so that the sensitivity to chemotherapy, targeted antibodies, immunotherapy and the like is improved, and the killing effect of the drug is improved. The invention also shows an excellent anti-tumor effect in a human tumor cell line xenotransplantation model of the drug-resistant breast cancer in vivo, and provides a promising treatment strategy for the treatment of the drug-resistant breast cancer.

To provide safe and effective compositions and methods for enhancing the efficacy and / or reducing the side effects of cancer chemotherapy and increasing the sensitivity of chemotherapy-resistant cancer cells.SOLUTION: Nutritional supplements comprising fish oil and selenium have been found to provide various activities that are beneficial in treating cancer and related conditions. The supplement provides a synergistic effect in reducing cancer cell growth when used in combination with a chemotherapeutic agent and can reduce growth in drug resistant cancer cells when used in combination with a chemotherapeutic agent to which the cells are resistant. Effects in reducing angiogenesis, reducing metastasis, decreasing the number of circulating cancer cells, and altering AXL signaling have also been found. The use of the supplement was found to reduce the wasting associated with cachexia and decrease circulating cytokines associated with inflammation. The overall effect was found to prolong survival in a clinical study.SELECTED DRAWING: Figure 1

The present invention relates to a composition for preventing or treating cancer having resistance to anticancer agents and, more specifically, to a pharmaceutical composition for preventing or treating resistant cancer, comprising a 3-ketoacyl CoA thiolase (ACAA) inhibitor and a carnitine acylcarnitine carrier (CAC) inhibitor and inhibiting the regrowth of cancer having resistance to anticancer agents. It is has been identified that the composition comprising the 3-ketoacyl CoA thiolase (ACAA) inhibitor and the carnitine acylcarnitine carrier (CAC) inhibitor, of the present invention, effectively inhibits the regrowth of cancer cells and tumors having resistance to various anticancer agents, and thus can be effectively used for the prevention or treatment of cancer having resistance to anticancer agents.

Disclosed herein are compositions comprising nanoparticles comprising a carrier polypeptide and a double-stranded oligonucleotide, wherein the carrier polypeptide comprises a cell-targeting segment, a cell-penetrating segment, and an oligonucleotide-binding segment; and wherein the molar ratio of the carrier polypeptide to the double-stranded oligonucleotide in the nanoparticle composition is less than about 6:1, along with methods of making and using such nanoparticles. Further described are methods of treating a subject with a cancer, such as a chemotherapeutic drug resistant cancer comprising administering to the subject a composition comprising nanoparticles, the nanoparticles comprising a carrier polypeptide comprising a cell-targeting segment, a cell-penetrating segment, and an oligonucleotide-binding segment; a double-stranded oligonucleotide bound to the oligonucleotide-binding segment; and a chemotherapeutic drug bound to the double-stranded oligonucleotide. Also described are pharmaceutical compositions, articles of manufacture, and kits comprising the described nanoparticles.

The present disclosure generally relates to compositions and methods for targeting pro-survival signaling hubs in anoikis-resistant cells, such as anoikis-resistant cancer cells. Embodiments also include methods of changing morphology of cells by inhibiting bleb formation which, in part, reduces survival of the cell and proliferation of the cell by disrupting downstream bleb-driven signaling.

An anti-human ROR1 antibody, an antibody-drug conjugate comprising the anti-human ROR1 antibody, and use for treating drug-resistant cancer.

The present invention provides, inter alia, methods, pharmaceutical compositions, and kits for treating or ameliorating the effects of a cancer in a subject, which cancer is refractory or resistant to non-ERK MAPK pathway inhibitor therapy. Also provided are methods for identifying a subject having cancer who would benefit from therapy with an ERK inhibitor and methods for inhibiting phosphorylation of RSK in a cancer cell that is refractory or resistant to a non-ERK MAPK pathway inhibitor.

Provided herein, inter alia, are compositions and methods comprising combination therapies including a BRAE axis inhibitor and a COX-2 inhibitor for the treatment of cancer. In embodiments, the combination therapies further include an EGER inhibitor. The combination therapies provided herein are particularly effective for treating BRAE intrinsically resistant cancers.

The present invention relates to a pharmaceutical composition for preventing or treating anticancer drug-resistant cancer, containing teriflunomide as an active ingredient, wherein the teriflunomide can function as an immune checkpoint inhibitor by blocking the binding of PD-1 and PD-L1, and thus can be effectively used in medicines for preventing or treating cancer. In addition, the teriflunomide according to the present invention has an excellent anticancer effect against uterine sarcoma cancer that is resistant to doxorubicin, and thus can be very effectively used for preventing or treating resistant cancer.

The inventors establish a role for primary cilia in human TNBC chemotherapeutic resistance. They developed patient-derived organoids, and showed that these recapitulated the cellular heterogeneity of TNBC biopsies. They treated their TNBC organoids with chemotherapeutics and observed partial killing. The surviving cells with organoid-reconstituting capacity showed selective enrichment for the quasi-mesenchymal ciliated cell subpopulation. They developed a family of small-molecule inhibitors of ciliogenesis and show that these, or genetic ablation of primary cilia, suppress chemoresistance. In particular, the present invention relates to a method of preventing therapeutic resistance in a patient suffering from a cancer comprising administering to the patient a therapeutically effective amount of an inhibitor of ciliogenesis. The present invention also relates to a method of treating a therapy-resistant cancer in a patient suffering from a cancer comprising administering to the patient a therapeutically effective amount of an inhibitor of ciliogenesis.

The present technology provides a combination approach for treating multidrug resistant cancer. Multidrug resistant cancers have more mitochondrial networks than drug sensitive cancers. A first agent fragments mitochondrial networks, dissociates mitochondria from the endoplasmic reticulum, and lower the threshold for apoptosis. A second active agent induces the unfolded protein response, causing stress to the endoplasmic reticulum and limiting the ability of multidrug resistant cancer cells to grow and survive. A third active agent directly activates mitochondrial apoptosis, leading to death of the cancer cells. The active agents can be combined into a nanoparticle formulation for simultaneous delivery into multidrug resistant cancer cells. The formulation serves as a nanomedicine for treatment of multidrug resistant cancers such as multidrug resistant triple negative breast cancer.

Pharmaceutical compositions and methods provide treatment of solid tumors based on simultaneously preventing the development and spread of multi-drug resistance (MDR) and a metastatic phenotype. This technology operates through the inhibition of two types of intercellular communication within the tumor microenvironment—tunneling nanotubes and extracellular vesicles, both of which promote the spread of MDR. Nanoparticle delivery of both an inhibitor of tunnelling nanotubes and an inhibitor of extracellular vesicle release work synergistically to trap and improve the effectiveness of anticancer drugs in cells of the tumor and permit the use of lower doses of anticancer drugs, with reduction in harmful side effects.

The present invention relates to a reduced graphene oxide nanocomposite for targeting multiple drug-resistant cancer cells capable of simultaneously performing enhanced photothermal therapy and photodynamic therapy, and a method for manufacturing the same. The nanocomposite of the present invention comprises reduced graphene, poly(N-isopropylacrylamide)-acrylic acid, and folic acid, thereby exhibiting excellent targeting function for multiple drug-resistant cancer cells. In particular, when an anticancer agent including indocyanine green is encapsulated internally, it exhibits a synergistic effect of photothermal and photodynamic therapy against multiple drug-resistant cancer.

Disclosed herein are methods of diagnosing tyrosine kinase inhibitor (TKI) resistant cancer and predicting response to TKI therapy in treatment. Also disclosed is a method of treating a TKI resistant cancer by administering a voltage gated potassium channel (VGKC) inhibitor. The disclosure also provides composition comprising a TKI and a VGKC inhibitor.