Provided herein are methods for determining the functional status of a cellular pathway in a diseased cell sample obtained from an individual subject. These methods involve contacting a diseased cell sample obtained from the subject with a perturbing agent (e.g., an activating agent) known to perturb a specific cellular pathway when the pathway is functioning normally. A change in one or more physiological response parameters in the presence of the perturbing agent indicates that the cellular pathway targeted by the perturbing agent is functional in the individual subject. Methods of selecting a targeted therapeutic agent for an individual subject are also provided.

Anti-EGFR antibodies, therapeutic compositions comprising combinations of anti-EGFR antibodies, as well as methods for using such antibodies and compositions to treat EGFR-related disorders (e.g., cancers), are disclosed.

The specification provides methods of determining whether a subject suffering from ER+/HER2+ breast cancer is likely to respond to adjuvant and neoadjuvant chemotherapy and methods of treating a subject suffering from ER+/HER2+ breast cancer.

The present invention relates to methods for the prediction of the progression of chronic kidney disease in a patient. More particularly, the invention relates to the early prediction of the fast progression of chronic kidney disease using specific biomarker signatures in urine sample of patients.

The current disclosure provides for specific peptides, and derived ionization characteristics of the peptides, from the Epidermal Growth Factor Receptor (EGFR) protein that are particularly advantageous for quantifying the EGFR protein directly in biological samples that have been fixed in formalin by the method of Selected Reaction Monitoring (SRM) mass spectrometry, or what can also be termed as Multiple Reaction Monitoring (MRM) mass spectrometry. Such biological samples are chemically preserved and fixed wherein said biological sample is selected from tissues and cells treated with formaldehyde containing agents/fixatives including formalin-fixed tissue/cells, formalin-fixed/paraffin embedded (FFPE) tissue/cells, FFPE tissue blocks and cells from those blocks, and tissue culture cells that have been formalin fixed and or paraffin embedded. A protein sample is prepared from said biological sample using the Liquid Tissue™ reagents and protocol and the EGFR protein is quantitated in the Liquid Tissue™ sample by the method of SRM/MRM mass spectrometry by quantitating in the protein sample at least one or more of the peptides described. These peptides can be quantitated if they reside in a modified or an unmodified form. An example of a modified form of an EGFR peptide is phosphorylation of a tyrosine, threonine, serine, and/or other amino acid residues within the peptide sequence.

An embodiment of the invention is a peptide comprising four domains, wherein domain I consists of thioctyl or monocytl, domain II consists of 2 to 3 positively charged amino acids selected from the group consisting of lysine and arginine, domain III consists of a dimeric ethylene unit; and domain IV comprises the peptide with SEQ ID No. 1 or a sequence having at least 90% identity to SEQ ID No. I. The peptide is preferably attached to a gold nanostructure, preferably a gold nanorod to provide an EFGR kit. An EFGR detection kit of the invention employs a gold nanostructure attached to a peptide sequence, the peptide sequence includes a binding sequence with an affinity toward EGFR, a ligand bound to gold atoms of the nanorod, a positively charged amino acid that maintains activity of the binding sequence, and a unit that increases hydrophilicity of the peptide sequence.

The invention relates to new identified mutations in the epidermal growth factor receptor gene, leading to amino acidic changes which highly correlate with the resistance to a therapy regimen comprising cetuximab. The invention includes peptide sequences and primers to detect the mutations, as well as kits for predicting the response of a subject to a therapy regime comprising cetuximab. In particular, the invention is useful in the therapy regimen applicable to metastasic colorectal cancer.

The invention relates to methods for predicting the in vivo nephrotoxicity of a drug substance, in particular a nucleic acid molecule such as a siRNA or an antisense oligonucleotide using an in vitro cell based assay measuring the levels of extracellular EGF as toxicity biomarker, potentially in combination with other biomarkers like ATP and KIM-1.

A method of diagnosing breast cancer is disclosed. The method comprises lysing extracellular vesicles of a subject to generate a composition comprising components of extracellular vesicles; measuring the amount of MEK1 in the composition; and diagnosing the subject with breast cancer when a level of said MEK1 in said composition is above a predetermined threshold. Kits for breast cancer diagnosis are also disclosed.

The invention provides anti-human pro-epiregulin and anti-human amphiregulin antibodies and methods of using the same. Anti-EREG antibodies raised against amino acids 148-169 and 156-169 of the human EREG protein, and anti-AREG antibodies raised against amino acids 238-252 of the human AREG protein are disclosed. Methods of using these antibodies to detect EREG and AREG and kits and other products for performing such methods are also disclosed.