Provided are a method for prediction of a response to a BCL2 family protein-targeting drug and a method for selection of a subject suitable for treatment with a BCL2 family protein-targeting drug.

The present invention relates to compositions and methods for treating cancer, particularly to agents that inhibit the expression and/or activity of the protein second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (SMAC/Diablo). The inhibiting agents include RNA interference molecules silencing the expression of SMAC/Diablo and peptides modulating its interactions within the cell nucleus and mitochondria. The methods and agents of the present invention are useful in treating cancers associated with overexpression of SMAC/Diablo.

The present invention relates to antisense oligonucleotides (oligomers) complementary to nucleic acids encoding mammalian T cell-restricted intracellular antigen-1 (TIA1), in particular antisense oligonucleotides targeting TIA1 pre-mRNA sequences, which are capable of inhibiting the expression of TIA1. Inhibition of TIA1expression is beneficial for a range of medical disorders including neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) or Frontotemporal Dementia.

The present invention relates to TWEAK-receptor agonists for use in the treatment of a cancer, wherein the TWEAK-receptor agonist is combined with immunotherapy of the cancer. The TWEAK-receptor agonist preferably is a multivalent ligand that causes clustering of TWEAK-receptors at the cell surface. A suitable TWEAK-receptor agonist is an agonistic anti-Fn14 antibody. The TWEAK-receptor agonist and immunotherapy be can further be combined with a SMAC mimetic in the treatment of cancer. The TWEAK-receptor agonist is useful, optionally in combination with a SMAC mimetic, to prevent resistance of a cancer to immunotherapy and/or to treat a cancer comprising tumor cells that are resistant to immunotherapy.

An amphiphilic fusion protein has a formula S/I—X—H.sub.1—H.sub.2, wherein S— is a solubilizing moiety, I— is an insolubilizing moiety, —X— is a peptide sequence comprising a proteolytic or chemical cleavage site, —H.sub.1— is a hydrophilic peptide, and —H.sub.2 is a hydrophobic peptide.

The present invention relates to interleukin-4 receptor binding fusion proteins. More specifically, the invention provides, in part, fusion proteins that include an interleukin-4 receptor binding protein moiety joined to a pro-apoptotic Bcl-2 family member protein moiety.

The present invention relates to interleukin-2 fusion proteins. More specifically, the invention provides, in part, fusion proteins that include a interleukin-2 protein moiety joined to a Bcl-2 family member protein moiety.

In one aspect, a method of treating a disorder associated with chronic inflammation includes administering to an individual in need thereof a therapeutically effective amount of isomyosmine or a pharmaceutically acceptable salt thereof. In some aspects, the disorder is a cancer, an autoimmune disorder, hypertension, or autism. In other aspects, isomyosmine is administered to treat viral infections or disorders associated with elevated levels of hydrogen peroxide and/or other Reactive Oxygen Species (ROS).

Identification of BAG3 (Bcl2-associated anthanogene 3) genetic variants were associated with the prevalence non-ischemic or ischemic dilated cardiomyopathy (DCM) and DCM outcomes in individuals of African ancestry.

Disclosed herein are methods and systems for determining microsatellite instability. In some embodiments, the disclosed methods and systems are used for determining whether a cancer patient has high microsatellite instability (MSI-H). MSI-H patients have remarkably good responses to immunotherapy, such as checkpoint inhibitors immunotherapy. Therefore, the disclosed methods and systems can be used for identifying MSI-H and thus, patients as candidates for immunotherapy. In turn, the disclosed methods and systems can be used to predict responsiveness to immunotherapy. In some embodiments, the methods further include providing an immunotherapy to the MSI-H patient. Also disclosed are vaccines and compositions.