Toll like receptor 4 dysfunction and the biological applications thereof
AssigneeInstitut Gustave Roussy
InventorsLionel Apetoh, Guido Kroemer, Laurence Zitvogel
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Abstract
The present invention relates to an in vitro method of assessing the sensitivity of a subject to a treatment of cancer, which method comprises detecting the presence of a mutated Toll Like Receptor 4 (TLR4) nucleic acid or an abnormal TLR4 protein expression or activity in a sample from the subject, the presence of said mutated TLR4 nucleic acid or abnormal TLR4 expression or activity being indicative of a resistance to said treatment. The invention further provides compounds for treating or preventing a cancer in a subject having a mutated TLR4 nucleic acid or an abnormal TLR4 protein expression or activity.
Claims30
An in vitro method of assessing the sensitivity of a subject having a cancer selected from breast cancer, sarcoma, ovarian cancer, endometrium cancer, bladder cancer, cervical cancer, prostate cancer, lung cancer, ORL cancer, paediatric tumours, neuroblastoma, glioblastoma multiforme, lymphoma, leukaemia, myeloma, seminoma, Hodgkin's lymphoma or malignant hemopathies to a chemotherapeutic treatment of said cancer comprising determining the presence of a mutated Toll Like Receptor 4 (TLR4) nucleic acid in a sample from the subject or determining the absence of TLR4 alleles in a sample from the subject, said mutated TLR4 nucleic acid being a wild-type TLR4 nucleic acid comprising a point mutation or a single nucleotide polymorphism (SNP) leading to the substitution of asparagine by glycine at position 299, wherein the presence of said mutated TLR4 nucleic acid or the absence of TLR4 alleles is indicative of a resistance to said chemotherapeutic treatment.
An in vitro method of assessing the sensitivity of a subject having a cancer selected from breast cancer, stomach cancer, sarcoma, ovarian cancer, endometrium cancer, bladder cancer, cervical cancer, prostate cancer, lung cancer, ORL cancer, paediatric tumours, neuroblastoma, glioblastoma multiforme, lymphoma, leukaemia, myeloma, seminoma, Hodgkin's lymphoma or malignant hemopathies to a chemotherapeutic treatment of said cancer comprising determining the presence of a mutated Toll Like Receptor 4 (TLR4) nucleic acid in a sample from the subject or determining the absence of TLR4 alleles in a sample from the subject, said mutated TLR4 nucleic acid being a wild-type TLR4 nucleic acid comprising a point mutation or a single nucleotide polymorphism (SNP) leading to the substitution of asparagine by glycine at position 299, wherein the presence of said mutated. TLR4nucleic acid or the absence of TLR4 alleles is indicative of a resistance to said chemotherapeutic treatment and treating a subject having a cancer selected from breast cancer, stomach cancer, sarcoma, ovarian cancer, endometrium cancer, bladder cancer, cervical cancer, prostate cancer, rectal cancer, lung cancer, ORL cancer, paediatric tumours, neuroblastoma, glioblastoma multiforme, lymphoma, leukaemia, myeloma, seminoma, Hodgkin's lymphoma or malignant hemopathies and whose cells lack TLR4 alleles or contain mutated TLR4 alleles with a composition comprising an alcalinizing lysosomotropic compound.
An in vitro method of assessing the sensitivity of a subject having a cancer selected from breast cancer, sarcoma, ovarian cancer, endometrium cancer, bladder cancer, cervical cancer, prostate cancer, lung cancer, ORL cancer, paediatric tumours, neuroblastoma, glioblastoma multiforme, lymphoma, leukaemia, myeloma, seminoma, Hodgkin's lymphoma or malignant hemopathies to a chemotherapeutic treatment of said cancer comprising determining the presence of a mutated Toll Like Receptor 4 (TLR4) nucleic acid in a sample from the subject or determining the absence of TLR4 alleles in a sample from the subject, said mutated TLR4nucleic acid being a wild-type TLR4 nucleic acid comprising a point mutation or a single nucleotide polymorphism (SNP) leading to the substitution of asparagine by glycine at position 299, wherein the presence of said mutated TLR4 nucleic acid or the absence of TLR4 alleles is indicative of a resistance to said chemotherapeutic treatment and treating a subject having a cancer selected from breast cancer, stomach cancer, sarcoma, ovarian cancer, endometrium cancer, bladder cancer, cervical cancer, prostate cancer, rectal cancer, lung cancer, ORL cancer, paediatric tumours, neuroblastoma, glioblastoma multiforme, lymphoma, leukaemia, myeloma, seminoma, Hodgkin's lymphoma or malignant hemopathies and whose cells contain unmutated TLR4 alleles with a chemotherapeutic treatment.
Dependencies are inferred from the claim text.