Provided herein are methods and systems of molecular profiling of diseases, such as cancer. In some embodiments, the molecular profiling can be used to identify treatments for a disease, such as treatments that were not initially identified as a treatment for the disease or not expected to be a treatment for a particular disease.

Acquisition of CD9 protein on the cell surface of NK cells confers an immunosuppressive phenotype to the NK cells, making them less effective in immunotherapy. CD9 can be transferred from tumor cells to NK cells present in the tumor environment through the process of trogocyotosis. Methods of enhancing NK cell anti-tumor activity can include evaluating NK receptor ligand expression within the tumor microenvironment(s) for patients eligible to receive NK cell immunotherapy.

A method of generating a classifier includes a step of classifying each member of a development set of samples with a class label in a binary classification scheme with a first classifier; and generating a second classifier using a classifier development process with an input classifier development set being the members of the development set assigned one of the two class labels in the binary classification scheme by the first classifier. The second classifier stratifies the members of the set with an early label into two further sub-groups. We also describe identifying a plurality of different clinical sub-groups within the development set based on the clinical data and for each of the different clinical sub-groups, conducting a classifier generation process for each of the clinical sub-groups thereby generating clinical subgroup classifiers. We further describe an example of a hierarchical arrangement of such classifiers and their use in predicting, in advance of treatment, ovarian cancer patient outcomes on platinum-based chemotherapy.

Heritable mutations in the BRCA1 and BRCA2 and other genes in the DNA double-strand break (DSB) repair pathway increase risk of breast, ovarian and other cancers. In response to DNA breaks, the proteins encoded by these genes bind to each other and are transported into the nucleus to form nuclear foci and initiate homologous recombination. Flow cytometry-based functional variant analyses (FVAs) were developed to determine whether variants in BRCA1 or other DSB repair genes disrupted the binding of BRCA1 to its protein partners, the phosphorylation of p53 or the transport of the BRCA1 complex to the nucleus in response to DNA damage. Each of these assays distinguished high-risk BRCA1 mutations from low-risk BRCA1 controls. Mutations in other DSB repair pathway genes produced molecular phenocopies with these assays. FVA assays may represent an adjunct to sequencing for categorizing VUS or may represent a stand-alone measure for assessing breast cancer risk.

The invention provides antibodies that specifically bind to an epitope containing N-acetylglucosamine or N-acetyl-galactosamine expressed by a cancer cell or an inflammatory cell. Also provided are compositions including these antibodies, as well as polynucleotides, vectors, host cells, and methods useful for production thereof. Further provided are methods and kits for treating or preventing cancer in an individual by administering to the individual an antibody that specifically binds to an epitope containing N-acetylglucosamine or N-acetyl-galactosamine, optionally in combination with another anti-cancer agent. Still further provided are methods and kits for treating or preventing gastrointestinal disease in an individual by administering to the individual an antibody that specifically binds to an epitope containing N-acetylglucosamine or N-acetyl-galactosamine. Yet further provided are methods and kits for detecting the presence of cancer cells in an individual including an antibody that specifically binds to an epitope containing N-acetylglucosamine and/or N-acetyl-galactosamine.

The disclosure provides for humanized antibodies, and fragments thereof, that are capable of binding to and killing human myeloma and ovarian cancer cells. The antibodies and their fragments are useful for therapeutic, diagnostic, and research purposes.

The inventors have identified several proteases and a protease inhibitor that are overexpressed in ovarian cancer tumors. They have developed monoclonal antibodies against the proteins and shown that they can be detected in serum and the levels of the proteins in serum fluctuate during cancer treatment. They have shown that serum assays for the proteases and protease inhibitor can be used for early detection of ovarian cancer, and for monitoring cancer treatment.

The present invention determined that EGFL6 functions as a tumor vascular regulator of ovarian cancer stem cells (CSC). In addition, the present invention determined that a novel EGFL6 blocking antibody was able to restrict cancer cell growth and delay disease recurrence. As such, the present invention provides compositions and methods for inhibiting cancer cell growth, proliferation and/or metastasis. In particular, the present invention provides methods for inhibiting cancer cell growth, proliferation and/or metastasis through administration of a composition comprising an agent capable of inhibiting the function of EGFL6 (e.g., thereby inhibiting related cancer cell growth). In some embodiments, the agent capable of inhibiting the function of EGFL6 is an EGFL6 blocking antibody. The agents and related compositions additionally find use in diagnostic and research settings.

Anti-tumour immune responses to modified self-epitopes. The present invention relates to the use of tumour-associated epitopes in medicine and in particular in the treatment of cancer. The epitopes stimulate an immune reaction against the tumour and have a modification selected from deimination of arginine to citrulline, nitration of tyrosine, oxidation of tryptophan and deamination of glutamine or asparagine. The invention also relates to nucleic acids comprising sequences that encode such epitopes for use in the treatment of cancer.

Methods are provided for predicting the presence, subtype and stage of ovarian cancer, as well as for assessing the therapeutic efficacy of a cancer treatment and determining whether a subject potentially is developing cancer. Associated test kits, computer and analytical systems as well as software and diagnostic models are also provided.