A p38 MAPK inhibitor for use in the treatment or prevention of severe influenza in a human patient. In some embodiments, the severe influenza maybe characterised by hypercytokinemia involving elevated levels of one or more pro-inflammatory cytokines. The p38 MAP kinase inhibitor may act to inhibit the release of such pro-inflammatory mediators from endothelial cells. In some embodiments, the p38 MAP kinase inhibitor may inhibit the release of IP 10 from endothelial cells, preferably in a dose-dependent manner.

The present invention relates to compositions and methods of inhibiting p38 kinase to reduce gene and protein expression of DUX4 and downstream genes regulated by DUX4. The present invention further relates to methods for treating patients suffering from diseases associated with increased expression of DUX4 or expression of an aberrant form of DUX4, such as Facioscapulohumeral muscular dystrophy (FSHD).

Provided herein are recombinant proteins comprising sets of polypeptides that may be used for measurement of protein levels.

Provided herein, inter alia, are p38 mitogen-activated protein kinase inhibitors and methods of treating cancer using p38 mitogen-activated protein kinase inhibitors.

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.

The present invention relates to compositions and methods of inhibiting p38 kinase to reduce gene and protein expression of DUX4 and downstream genes regulated by DUX4. The present invention further relates to methods for treating patients suffering from diseases associated with increased expression of DUX4 or expression of an aberrant form of DUX4, such as Facioscapulohumeral muscular dystrophy (FSHD).

A p38 MAPK inhibitor for use in the treatment or prevention of severe influenza in a human patient. In some embodiments, the severe influenza may be characterised by hypercytokinemia involving elevated levels of one or more pro-inflammatory cytokines. The p38 MAP kinase inhibitor may act to inhibit the release of such pro-inflammatory mediators from endothelial cells. In some embodiments, the p38 MAP kinase inhibitor may inhibit the release of IP 10 from endothelial cells, preferably in a dose-dependent manner.

The disclosure relates to methods and compositions including p38 kinase inhibitors and agents that regulate expression of DUX4 and downstream genes including but not restricted to ZSCAN4, LEUTX, PRAMEF2, TRIM43, MBD3L2, KHDC1L, RFPL2, CCNA1, SLC34A2, TPRX1, PRAMEF20, TRIM49, PRAMEF4, PRAME6, PRAMEF15, or ZNF280A. Methods useful for treating a disease associated with abnormal DUX4 and downstream gene expression (e.g., Fascioscapulohumeral muscular dystrophy) are disclosed.

The present invention relates to an in vitro method which enables the prediction of therapeutic response to treatment with BRAF inhibitor drugs, such as vemurafenib, in cancer patients associated with oncogenic mutations in said kinase, such as BRAF positive melanoma. Said method is based on the measurement of cytoplasmic ERK1/2 levels through the detection and quantification of ERK1/2 phosphorylated in serine 301/284, respectively, in an isolated biological sample of the patient. The invention also provides a specific antibody against ERK1/2 phosphorylated in serine 301/284 and a kit comprising it, which are of use in the described method.

The disclosure relates to methods and compositions including p38 kinase inhibitors and agents that regulate expression of DUX4 and downstream genes including but not restricted to ZSCAN4, LEUTX, PRAMEF2, TRIM43, MBD3L2, KHDC1L, RFPL2, CCNA1, SLC34A2, TPRX1, PRAMEF20, TRIM49, PRAMEF4, PRAME6, PRAMEF15, or ZNF280A. Methods useful for treating a disease associated with abnormal DUX4 and downstream gene expression (e.g., Fascioscapulohumeral muscular dystrophy) are disclosed.