The present invention relates to a non-agonist ligand of ARTC1, which inhibits the ADP-ribosyltransferase activity of ARTC1, or an inhibitor nucleic acid sequence capable of downregulating or inhibiting expression of a target nucleic acid sequence encoding ARTC1, for use in prevention or treatment of cancer. The invention also relates to a method for diagnosis of cancer.

The present disclosure is related to methods of identifying Poly(ADP-ribose) polymerases (PARP) inhibitors, and the methods of using PARP probes.

The present disclosure is related to methods of identifying Poly(ADP-ribose) polymerases (PARP) inhibitors, and the methods of using PARP probes.

There are provided, inter alia, methods and reagents for labeling nucleic acids.

It is an aim of the present invention to provide inhibitors of human diphtheria toxin-like ADP-ribosyltransferases, such as ARTD10, for use as a medicine. It is another aim of the invention to provide compounds for use as human mono-ADP-ribosyltransferase (mARTD) inhibitors in vitro. In the present invention, it has been discovered that human ARTD10, which belongs to an enzyme family linked to cancer biology, can be specifically inhibited by the benzamide comprising compounds disclosed in the invention, such as 4,4′-oxydibenzamide.

Poly(ADP-ribose) (PAR) is a protein implicated in numerous neurodegenerative disease states including Parkinson's disease (PD). To date, no routine laboratory test has been developed to diagnosis, assess or monitor patients suffering from PD. Disclosed herein a novel method to assess the PAR concentration in the cerebral spinal fluid (CSF) of a patient and correlate that concentration to the medical condition of a patient with PD. Also disclosed is the use of PAR as a biomarker for PD.

The present invention relates to a method for treating a subject suffering from melanoma resistant by administering to said subject an inhibitor of NAMPT. Using a global metabolic profiling, inventors have showed that in addition to glycolysis, the BRAF inhibitor, PLX4032, promoted a complex metabolic rewiring of melanoma cells, including protein catabolism and fatty acid synthesis. Importantly, they observed that PLX4032 reduced the levels of nicotinamide adenine dinucleotide (NAD+), an important redox co-factor in numerous metabolic processes, including glycolysis, tricarboxylic acid cycle (TCA) cycle, glutamate metabolism and fatty acid betaoxidation. Pharmacological or genetic inhibition of NAMPT impaired melanoma cell growth, whereas the overexpression of NAMPT dampened the antiproliferative effect of PLX4032. In vivo, the inhibition of NAMPT also prevented the xenograft development of PLX4032-sensitive and -resistant melanoma cells, identifying NAMPT as a potential target for BRAFi-resistant melanomas.

The present invention is related to diagnostic, treatment and compound screening methods related to dry age-related macular degeneration (dry AM D). In select embodiments, the methods comprise determining expression or activity levels of NAD-dependent deacetylase sirtuin-1 (SI RT-1), AM P-activated protein kinase (AM PK), poly(adenosine diphosphate ribose) polymerase-2 (PARP2), peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-I) and/or mRNA levels of RAC-gamma serine/threonine-protein kinase (AKT3). In general, higher levels of PARP2, lower levels of PGC-I or AKT3 and/or higher acetylation levels of PGC-I in the samples are indicative that the subject or cells from which the samples are obtained are susceptible or are suffering from dry AMD.

Disclosed herein are methods for treating subjects with breast cancer, comprising determining a therapeutic regimen for cancer by measuring the level (amount) of proteins of one or more biomarkers. Also disclosed are methods of treating a subject with breast cancer by predicting or assessing a therapeutic outcome for subject.

Improved methods for treating cancer are provided herein by determining if a cancer patient, particularly a colon cancer patient or a gastric cancer patient, will clinically respond in a favorable manner to a therapeutic strategy comprising the FOLFOX regimen (fluorouracil, leucovorin, and oxaliplatin) or a combination of capecitabine and cisplatin. Diagnostic methods for measuring the OPRT, TYMP, and/or UCK2 proteins in a tissue sample, such as a tumor sample, from the patient are provided.