Abstract: Described herein are compositions and methods of using single-cell RNA-sequencing to identify treatment resistance in patients with ovarian cancer. Also, described herein are compositions and methods for treatment targeting resistance in patients with ovarian cancer.

Abstract: An isolated nucleic acid molecule encoding a mutant MEK1 protein having MEK1 activity is disclosed. The mutant MEK1 protein comprises an amino acid substitution at position 121 of wild-type MEK1 shown in SEQ ID NO: 2. The amino acid substitution confers resistance to one or more RAF or MEK inhibitors on a cell expressing the mutant MEK1 protein.

Abstract: Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

Abstract: Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

Abstract: Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

Abstract: The invention provides methods and devices for determining molecular signatures in a cancer that predict response to a MARPK pathway inhibitor and methods of use of such signatures.

Abstract: A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.

Abstract: Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

Abstract: Isolated mutant ERK polypeptides and nucleic acids encoding the mutant ERK polypeptides are provided. Methods of screening cancer-containing samples for an ERK polypeptide mutation that confers resistance to treatment with a first MAPK pathway inhibitor are provided. Methods of optimizing treatment of a subject having cancer and methods of identifying compounds useful in treating cancer are also provided.

Abstract: The invention provides methods and devices for determining molecular signatures in a cancer that predict response to a MARPK pathway inhibitor and methods of use of such signatures.

Abstract: A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.

Abstract: The invention provides methods and devices for determining molecular signatures in a cancer that predict response to a MARPK pathway inhibitor and methods of use of such signatures.

Abstract: Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

Abstract: Described herein are compositions and methods of using single-cell RNA-sequencing to identify treatment resistance in patients with ovarian cancer. Also, described herein are compositions and methods for treatment targeting resistance in patients with ovarian cancer.

Abstract: Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

Abstract: The present invention provides methods for introducing mutations to primary cells and selecting for the mutations to obtain a population of cells for modeling cancer. Such methods may comprise at least one round of introducing one or more mutations into one or more cells in a population of cells in vitro and culturing the cells until the mutation(s) are positively selected in the population. The cells may be cultured in vitro. The cells may be cultured in vivo. In certain embodiments, the cells are positively selected in vivo in order to select for cells capable of evading the immune system. In certain embodiments, cells are selected in an immune competent animal model. The cells may primary cells. The population of cells may be used for drug screening and for studying cancer.

Abstract: Described herein are compositions and methods of disaggregating a tissue sample into single cells.

Abstract: Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

Abstract: The present invention generally relates to therapeutic inhibition of protein arginine methyltransferase 5 (PRMT5). In particular, cell lines having MTAP loss and increased intracellular MTA concentrations show selective dependence on PRMT5. Thus, the invention also relates to methods of identifying and treating PRMT5-related diseases in subjects or tissues which have an MTAP deficiency, alone or in combination, with a second agent that reduces MTAP activity and/or increases intracellular MTA levels, and/or provides an MTA analogs to the cell or tissue. The invention also relates to the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas System and components thereof. More specifically, the present invention relates to the delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions in tumor cells ex vivo and/or in vivo. For example using methods disclosed herein, cells can be sensitized to PRMT5 inhibition.

Abstract: Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.