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 the disease, such as treatments that provide likely benefit or likely lack of benefit for the disease.

The present invention provides a method for diagnosing and determining prognosis of gastric cancer in a subject by detecting suppressed expression of the REC8 gene, which in some cases is due to elevated methylation level in the genomic sequence of this gene. A kit and device useful for such a method are also provided. In addition, the present invention provides a method for treating gastric cancer by increasing REC8 gene expression or activity. Lastly, a highly sensitive and accurate detection method is provided for rapid determination of REC8 gene methylation status.

Biodegradable fluorescent silica nanoparticle (FSN) are provided for in vivo imaging, particularly of cancerous and precancerous lesions in the gastrointestinal tract. The FSN are comprised of (a) a dye that fluoresces in the near infrared spectrum which is (i) covalently joined to a silane, and (ii) distributed throughout the nanoparticle; and (b) silica distributed throughout the nanoparticle. The surface may be coated with hydroxyl-terminated PEG, which is shown to reduce uptake of the nanoparticles by the liver. The dyes provide for sensitive detection of clinically relevant lesions, and are biodegradable.

The present invention provides an in-vitro process for profiling a combined expression pattern of SATB (special AT-rich sequence-binding protein-1) family chromatin organizers i.e. SATB-1 and SATB-2 as a biomarker tool for cancer prognosis to assess cancer aggressiveness and it progression in an array of cancer types. The combined expression pattern of SATB is established by the method of Kaplan Meier survival analysis of a dataset of patients from a plurality of cancer types. Further, the present invention provides a prognostic kit to evaluate the progression of cancer by using the combined expression pattern of SATB-1 and SATB-2 as a biomarker tool for cancer prognosis.

The present invention relates generally to a method of determining one or more probabilities of respective classifications of a neoplasm into one or more neoplastic categories. More particularly, the present invention relates to a method of determining the probability of classification of a large intestine neoplasm into one or more categories selected from adenoma, stage I, stage II, stage III or stage IV by screening for changes to the methylation levels of a panel of gene markers, including BCAT1, IKZF1, IRF4, GRASP and/or CAHM. The method of the present invention is useful in a range of applications including, but not limited to, those relating to the diagnosis and/or monitoring of colorectal neoplasms, such as colorectal adenocarcinosis.

The present invention is directed to a combination therapy involving an anti-HER2 antibody-drug conjugate and a selective Bcl-2 inhibitor for the treatment of a patient suffering from cancer, particularly, a HER2-expressing cancer.

The present invention provides a method for evaluating the risk of occurrence of cancer in an individual.

The present invention relates to a biomarker composition for predicting the prognosis of cancer malignancy induced by exposure to microplastics and use thereof, and more particularly, it was confirmed that the expression level of CD44, E-cadherin, N-cadherin, PD-L1, NPAS2, NR1D1, DNMT1, SLC7A2, PCDH7 and CLDN7 was changed in cancer cell lines and animal models treated with polystyrene microspheres which are the one type of microplastic for 4 weeks, and malignancy was induced due to an increase in proliferation, migration and invasion of cancer cells by the change in the expression level of the gene, and 5-year overall survival rates in gastric cancer patients decreased and thus the genes may be provided as a biomarker composition for predicting the prognosis of cancer malignancies by exposure to microplastics.

Described herein are high affinity antigen binding constructs, e.g., antibodies, directed to the ECD2 domain of HER2. The antigen-binding constructs comprise at least one antigen-binding polypeptide construct that binds to ECD2 of HER2 (HER2 ECD2) with increased affinity compared to a wild-type 2C4 antibody. Such antigen-binding polypeptide constructs comprise one or more amino acid modifications in the framework region and/or CDRs compared to the amino acid sequence of a wild-type 2C4 antibody that increase affinity of the antigen-binding polypeptide construct for ECD2 by 2-fold or greater. The antigen-binding constructs can inhibit the growth of HER2-expressing breast cancer cells and gastric cancer cells. Antigen-binding constructs in biparatopic format are internalized in HER2-expressing cells.

The disclosure provides novel personalized therapies, kits, transmittable forms of information and methods for use in treating patients having cancer, wherein the cancer is amenable to therapeutic treatment with an inhibitor, e.g., an inhibitor of any of the targets disclosed herein. Kits, methods of screening for candidate inhibitors, and associated methods of treatment are also provided.