Induction of cellular lethality in cancer
OwnerSérgio Fernandes De Almeida, Cristiana Marisa De Sousa Morgado +1inventors
InventorsSérgio Fernandes De Almeida, Cristiana Marisa De Sousa Morgado, Claus Maria Azzalin
Life of this patent
Estimating the term…
Abstract
The present invention relates to the finding that depletion of a FANC protein or gene, such as FANCM, FANCD2 or FANCI, causes synthetic lethality in SETD2 deficient cells. Methods and compounds for use in the treatment of SETD2 deficient cancers are provided.
Claims56
A method of treatment of a cancer in an individual in need thereof comprising;
- reducing the expression or activity of a Fanconi anaemia, complementation group (FANC) protein in the individual, wherein the cancer is SETD2 deficient.
A method according to any one of the preceding claims, wherein the SETD2 deficient cancer is selected from the group consisting of leukaemia, such as AML, CML, ALL and CLL, lymphoma, such as Hodgkin lymphoma, non-Hodgkin lymphoma and multiple myeloma, and solid cancers such as sarcomas;
- skin cancer;
- melanoma, bladder cancer;
- brain cancer, such as glioblastoma multiforme, such as paediatric glioblastoma multiforme;
- breast cancer;
- uterus cancer;
- oral cancer;
- ovary cancer;
- prostate cancer;
- lung cancer, such as lung adenocarcinoma, and lung squamous cell carcinoma;
- colorectal cancer;
- cervical cancer;
- liver cancer;
- head and neck cancer;
- oesophageal cancer;
- pancreas cancer;
- renal cancer, such as clear cell renal cancer;
- stomach cancer;
- testicular cancer;
- cancer of the gall bladder and biliary tracts;
- thyroid cancer;
- thymus cancer;
- cancer of bone;
- and cerebral cancer.
A method according to any one of the preceding claims wherein the SETD2 deficient cancer comprises one or more cancer cells with a mutation in SETD2 or loss of SETD2.
A method according to any one of the preceding claims, the method further comprising a step of identifying an individual as having a cancer deficient in SETD2.
A method according to any one of the preceding claims, the method further comprising administering a chemotherapeutic agent to the individual.
A FANC antagonist for use in a method of treatment of a SETD2 deficient cancer.
Use of a FANC antagonist in the manufacture of a medicament for treatment of a SETD2 deficient cancer.
A method of screening for a compound that induces cell death in SETD2 deficient cancer cells, comprising determining the binding of a test compound to a FANC protein, wherein binding to FANC protein is indicative that the compound induces cells death in SETD2 deficient cells.
A method of screening for a compound that induces cell death in SET2D deficient cancer cells comprising determining the effect of a test compound on the expression or activity of FANC protein, wherein reduction in expression or activity of FANC protein is indicative that the compound induces cell death in SETD2 deficient cancer cells.
A method of determining responsiveness of a cancer in an individual to treatment with a FANC antagonist comprising determining the presence of one or more SETD2 deficient cells in a sample obtained from the individual, the presence of one or more SETD2 deficient cancer cells in the sample being indicative that the cancer is responsive to the treatment with the FANC antagonist.
A method of selecting an individual having a SETD2 deficient cancer for treatment with a FANC antagonist, the method comprising;
- identifying a cancer cell obtained from the individual as deficient in SETD2 relative to normal cells.
Dependencies are inferred from the claim text.