Provided herein are compositions and methods for the treatment of cancer by activating the spindle assembly checkpoint (SAC) in cells. In particular, dimerized Mps1 and Spc105/KNL1 constructs are provided as tunable activators of SAC, allowing for control of chromosome segregation accuracy and prevention of aneuploidies that are common in cancer.

Provided herein are compositions and methods for the treatment of cancer by activating the spindle assembly checkpoint (SAC) in cells. In particular, dimerized Mps1 and Spc105/KNL1 constructs are provided as tunable activators of SAC, allowing for control of chromosome segregation accuracy and prevention of aneuploidies that are common in cancer.

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.

Provided herein are compositions and methods for the treatment of cancer by activating the spindle assembly checkpoint (SAC) in cells. In particular, dimerized Mps1 and Spc105/KNL1 constructs are provided as tunable activators of SAC, allowing for control of chromosome segregation accuracy and prevention of aneuploidies that are common in cancer.

The presently disclosed subject matter is directed to dual specificity mitogen-activated protein kinase phosphatase (DUSP-MKP) inhibitors that sensitize cancer cells immune cell killing and methods of using the disclosed DUSP-MKP inhibitors for the treatment of cancer.

Disclosed herein are methods of treating or preventing the development of osteoarthritis after a joint injury by administering a CD14 inhibitor capable of neutralizing or blocking CD14, inhibiting CD14 function, inhibiting CD14 production, or a combination thereof. Also disclosed herein are methods of reducing or ameliorating one or more symptoms of osteoarthritis, reducing inflammation, reducing cartilage degradation, or treating or preventing subchondral bone sclerosis in a subject.

The invention relates to a method of increasing the resistance to one or more pathogens, preferably fungal or bacterial pathogens, in a monocotyledonous or dicotyledonous plant or a part of a plant, for example in an organ, tissue, a cell or a part of a plant cell, for example in an organelle, wherein a DNA sequence which codes for YODA protein or wherein an endogenous DNA sequence which codes for a YODA protein is increased in the plant or plant cell in comparison with the original, or wild-type, plant. The invention also relates to plants, to parts of a plant, for example an organ, tissue, a cell or a part of a plant cell, for example an organelle, which are obtained by the above methods, and to the corresponding propagation material.

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.

The use of mitogen activated kinase inhibition therapy in combination with receptor tyrosine kinase therapy for the treatment of cancer is described.

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.