The present invention provides nucleic acids encoding a fusion protein comprising a nucleotide sequence encoding GRIM-19 or a biologically active fragment or derivative thereof and a nucleotide sequence encoding a protein transduction domain. Proteins encoded by the nucleic acids, pharmaceutical compositions and methods of treatment are also provided. The invention also provides viral vectors comprising GRIM-19 or a biologically active fragment or derivative thereof, pharmaceutical compositions and methods of treatment using the same.

The present disclosure relates to a Proteomics-to-Genomics approach allows for in silico validation of biomarkers and drug targets. Biomarkers having high prognostic value in predicting cancer patient populations that may benefit from mitochondrial biogenesis inhibitor therapy may be identified under the present approach. Also disclosed are methods for identifying candidates for anti-mitochondrial therapy, and in particular mitochondrial biogenesis inhibitor therapy. Diagnostic kits including reagents for determining transcripts or probes of high prognostic value are also disclosed. Additionally, mitochondrial biogenesis inhibitors may be used as anti-cancer agents for diverse oncogenic stimuli, including for example, c-MYC and H-Ras oncogenes, as well as environmental stimuli such as, for example rotenone.

The method for preventing progression to Type II Diabetes includes determining whether a subject possesses a risk variant expression profile demonstrating dysregulation of the IL-33/ST2 axis, and providing an intervention to prevent progression to Type II Diabetes and/or to reverse prediabetes, including modifications of diet and exercise, administration of one or more pharmaceutical compounds, or a combination thereof. The method may be useful to reduce the risk of developing complications associated with Type II Diabetes or prediabetes, such as heart disease, stroke, or obesity. The pharmaceutical compound may be one or more pharmaceuticals capable of reducing circulating cholesterol, reducing blood glucose levels, reducing blood pressure, or a combination thereof.

The present invention generally relates to a method of diagnosing, prognosing and treating prostate cancer patients. Particularly, the present invention relates to a method of selecting patients with castration resistant prostate cancer (CrPC) for combination therapy comprising a selective dipeptidyl peptidase inhibitor and a PD-1 axis antagonist. The present invention provides a computational approach to identifying potential patients for CrPC. The present invention also relates to a method of treating castration resistant prostate cancer (CrPC) patients with said combination therapy.

The present invention relates to methods for diagnosing, staging and treating cancer, in particular melanoma. In particular, the present invention provides methods for determining the stage/type of a cancerous disease, comprising detecting somatic alterations of the DNA of one or more disseminated cancer cells (DCCs), obtained after homing to a distant organ, such as lymph node; and determining the somatic evolution of the DCC(s) based on the detected somatic alterations, wherein the somatic evolution is indicative of the stage/type of the cancerous disease.

The present invention belongs to the field of diagnosis of disease. Thus the present invention is focused on a method and kit and system for quantifying the level of minimal residual disease (MRD) in a subject who has been treated for said disease, as well as a method of treatment of said disease in a subject which comprises a step of quantifying the level of minimal residual diseases, wherein said quantifying comprises: (a) identifying, amplifying and sequencing a nucleotide sequence in a biological sample obtained from said subject after treatment for said disease, wherein the gDNA of said biological sample has an average weight, k, per cell, and wherein said nucleotide sequence is identified using primers and is amplified using an amount, D, to afford a first list of characters; (b) identifying, amplifying and sequencing a nucleotide sequence in a biological sample obtained from a subject with said disease using the same primers as in step (a) to afford a second list of characters; (c) determining, for each first list of characters obtained in step (a), the degree of similarity, DS, with each second list of characters obtained in step (b); (d) selecting, for each first list of characters obtained in step (a), the DS of highest value, DS.sub.HV; (e) adding up the number of first lists of characters obtained in step (a) which have a DS.sub.HV that is greater than a threshold value, T, to obtain L.sub.c; (f) adding up the total number of lists of characters, L.sub.t, in the first list of characters; and (g) calculating the level of minimal residual disease (MRD) according to either of the following formulae:
MRD=(L.sub.c×k)/(L.sub.t×D)
or
MRD=L.sub.c/L.sub.t
or
MRD=L.sub.c×(D/k)/L.sub.t.sup.2.

The present invention relates to a biomarker composition for predicting the prognosis of a cancer patient, the biomarker composition including a first molecular subtype or a protein transcribed and translated from the first molecular subtype. The present invention also relates to a biomarker composition for predicting the prognosis of a cancer patient, the biomarker composition further including a second molecular subtype or a protein transcribed and translated from the second molecular subtype.

Methods for detection, diagnosis, prognosis, theragnosis, and targeted therapy of a PRSS21-overexpressing condition (e.g., cancer), in particular, PRSS21-overexpressing acute myeloid leukemia of the AMKL subtype.

Disclosed herein, in certain instances, are methods, systems and kits for the diagnosis, prognosis and determination of cancer progression of a cancer in a subject. Further disclosed herein, in certain instances, are methods, systems and kits for determining the treatment modality of a cancer in a subject. The methods, systems and kits comprise expression-based analysis of biomarkers. Further disclosed herein, in certain instances, are probe sets for use in assessing a cancer status in a subject. Further disclosed herein are classifiers for analyzing a cancer.

The invention provides methods and compositions to detect expression of one or more biomarkers, including FGFR3, TP53, and/or EGFR, for treating, diagnosing, and providing a prognosis for cancer, e.g., bladder cancer. The invention also provides kits and articles of manufacture for use in the methods.