Abstract: Human induced pluripotent stem cells (iPSCs) can give rise to multiple cell types and hold great promise in regenerative medicine and disease modeling applications. The Inventors herein developed a reliable two-step protocol to generate human mammary-like organoids from iPSCs. Non-neural ectoderm cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. Gene expression profile analysis suggested that mammary gland function-associated signaling pathways were hallmarks of 10-d differentiated mEBs. The Inventors generated mammary-like organoids from 10-d mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. These organoids expressed common breast tissue, luminal, and basal markers, including estrogen receptor, and could be induced to produce milk protein. These results demonstrate that human iPSCs can be directed in vitro toward mammary lineage differentiation.

Abstract: Described herein are reprogramming techniques allowing for production of mammary-derived iPSCs (“m-iPSCs”). The m-iPSCs described herein exhibit all the hallmarks of stem cell identity including round cluster, bright colony morphology, clonal expansion, and pluripotent marker expression (alkaline phosphatase expression, Oct-4, nanog, etc.) Further refined techniques allow for generation of m-iPSCs under essentially defined conditions.

Abstract: In one embodiment, methods of theranostic classification of a breast cancer tumor are provided, wherein the classification is determined by detecting an expression level of FOXC1. In other embodiments, methods for predicting a prognosis of a basal-like breast cancer and methods of treating a basal-like breast cancer are provided. In other embodiments, methods for diagnosing metastatic breast cancer using the expression ratio of FOXC1/FOXA1 in a population of breast cancer tumor cells are provided. The methods also entail administering a treatment for metastatic breast cancer if the expression ratio of FOXC1/FOXA1 in the population of breast cancer tumor cells is elevated as compared to a control. Other embodiments provide methods for treating breast cancer with a proteasome inhibitor alone or in combination with a Wnt inhibitor in subjects with tumor cells expressing FOXC1 in a subject.

Abstract: Described herein are reprogramming techniques allowing for production of mammary-derived iPSCs (“m-iPSCs”). The m-iPSCs described herein exhibit all the hallmarks of stem cell identity including round cluster, bright colony morphology, clonal expansion, and pluripotent marker expression (alkaline phosphatase expression, Oct-4, nanog, etc.) Further refined techniques allow for generation of m-iPSCs under essentially defined conditions.

Abstract: In one embodiment, an isolated antibody or functional fragment thereof which binds an antigenic peptide sequence of human FOXC1 is provided herein. Such antibodies or functional fragments may be used to diagnose, prognose or treat basal-like breast cancer. The antibody or functional fragment may be a monoclonal antibody produced by a hybridoma cell line. Thus, a hybridoma cell line that produces a FOXC1 monoclonal antibody which binds an antigenic peptide sequence of human FOXC1 as described above is also provided.

Abstract: Human induced pluripotent stem cells (iPSCs) can give rise to multiple cell types and hold great promise in regenerative medicine and disease modeling applications. The Inventors herein developed a reliable two-step protocol to generate human mammary-like organoids from iPSCs. Non-neural ectoderm cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. Gene expression profile analysis suggested that mammary gland function-associated signaling pathways were hallmarks of 10-d differentiated mEBs. The Inventors generated mammary-like organoids from 10-d mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. These organoids expressed common breast tissue, luminal, and basal markers, including estrogen receptor, and could be induced to produce milk protein. These results demonstrate that human iPSCs can be directed in vitro toward mammary lineage differentiation.

Abstract: Described herein are gene signatures providing prognostic, diagnostic, treatment and molecular subtype classifications of ovarian cancers through generation of ovarian cancer disease signatures (OCDSs) that account for molecular heterogeneity present in gynecological cancers. An ovarian cancer fixed signature (OCFS) is described which relates to the core programming of disease development, in addition to an ovarian cancer stem cell (OCSC) signature. Development various disease signature, suggests personalized treatment strategies focused on molecular subtypes of gynecological cancers, such as triage tests for patients.

Abstract: In one embodiment, methods of theranostic classification of a breast cancer tumor are provided, wherein the classification is determined by detecting an expression level of FOXC1. In other embodiments, methods for predicting a prognosis of a basal-like breast cancer and methods of treating a basal-like breast cancer are provided. In other embodiments, methods for diagnosing metastatic breast cancer using the expression ratio of FOXC1/FOXA1 in a population of breast cancer tumor cells are provided. The methods also entail administering a treatment for metastatic breast cancer if the expression ratio of FOXC1/FOXA1 in the population of breast cancer tumor cells is elevated as compared to a control. Other embodiments provide methods for treating breast cancer with a proteasome inhibitor alone or in combination with a Wnt inhibitor in subjects with tumor cells expressing FOXC1 in a subject.

Abstract: Disclosed herein are methods of treating cancer in a patient, the method comprising identifying a patient who is resistant to treatment with an anti-HER2 therapy; and administering to the patient a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; a nucleic acid molecule bound to the polypeptide sequence via electrostatic interactions; and a chemical agent non-covalently linked to the nucleic acid sequence. Also disclosed are methods of inducing apoptosis in an anti-HER2 therapy resistant HER2+ breast cancer cell, the method comprising contacting the anti-HER2 therapy resistant HER2+ breast cancer cell with the drug delivery molecule.

Abstract: Disclosed herein are methods of treating cancer in a patient, the method comprising identifying a patient who is resistant to treatment with an anti-HER2 therapy; and administering to the patient a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; a nucleic acid molecule bound to the polypeptide sequence via electrostatic interactions; and a chemical agent non-covalently linked to the nucleic acid sequence. Also disclosed are methods of inducing apoptosis in an anti-HER2 therapy resistant HER2+ breast cancer cell, the method comprising contacting the anti-HER2 therapy resistant HER2+ breast cancer cell with the drug delivery molecule.

Abstract: In one embodiment, an isolated antibody or functional fragment thereof which binds an antigenic peptide sequence of human FOXC1 is provided herein. Such antibodies or functional fragments may be used to diagnose, prognose or treat basal-like breast cancer. The antibody or functional fragment may be a monoclonal antibody produced by a hybridoma cell line. Thus, a hybridoma cell line that produces a FOXC1 monoclonal antibody which binds an antigenic peptide sequence of human FOXC1 as described above is also provided.

Abstract: Described herein are reprogramming techniques allowing for production of mammary-derived iPSCs (“m-iPSCs”). The m-iPSCs described herein exhibit all the hallmarks of stem cell identity including round cluster, bright colony morphology, clonal expansion, and pluripotent marker expression (alkaline phosphatase expression, Oct-4, nanog, etc.) Further refined techniques allow for generation of m-iPSCs under essentially defined conditions.

Abstract: Disclosed herein are methods of treating cancer in a patient, the method comprising identifying a patient who is resistant to treatment with an anti-HER2 therapy; and administering to the patient a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; a nucleic acid molecule bound to the polypeptide sequence via electrostatic interactions; and a chemical agent non-covalently linked to the nucleic acid sequence. Also disclosed are methods of inducing apoptosis in an anti-HER2 therapy resistant HER2+ breast cancer cell, the method comprising contacting the anti-HER2 therapy resistant HER2+ breast cancer cell with the drug delivery molecule.

Abstract: In one embodiment, a method of theranostic classification of a breast cancer tumor is provided, comprising obtaining a breast cancer tumor sample from a subject, detecting an expression level of FOXC1, comparing the expression level of FOXC1 to a predetermined cutoff level, and classifying the breast cancer tumor sample as belonging to a theranostic basal-like breast cancer tumor subtype or a theranostic hybrid basal-like breast cancer tumor subtype when the expression level of FOXC1 is higher than the predetermined cutoff level.

Abstract: Described herein are gene signatures providing prognostic, diagnostic, treatment and molecular subtype classifications of ovarian cancers through generation of ovarian cancer disease signatures (OCDSs) that account for molecular heterogeneity present in gynecological cancers. An ovarian cancer fixed signature (OCFS) is described which relates to the core programming of disease development, in addition to an ovarian cancer stem cell (OCSC) signature. Development various disease signature, suggests personalized treatment strategies focused on molecular subtypes of gynecological cancers, such as triage tests for patients.

Abstract: In one embodiment, a method of theranostic classification of a breast cancer tumor is provided, comprising obtaining a breast cancer tumor sample from a subject, detecting an expression level of FOXC1, comparing the expression level of FOXC1 to a predetermined cutoff level, and classifying the breast cancer tumor sample as belonging to a theranostic basal-like breast cancer tumor subtype or a theranostic hybrid basal-like breast cancer tumor subtype when the expression level of FOXC1 is higher than the predetermined cutoff level. In other embodiments, methods for predicting a prognosis of a basal-like breast cancer and methods of treating a basal-like breast cancer are provided.

Abstract: In one embodiment, an isolated antibody or functional fragment thereof which binds an antigenic peptide sequence of human FOXC1 is provided herein. Such antibodies or functional fragments may be used to diagnose, prognose or treat basal-like breast cancer. The antibody or functional fragment may be a monoclonal antibody produced by a hybridoma cell line. Thus, a hybridoma cell line that produces a FOXC1 monoclonal antibody which binds an antigenic peptide sequence of human FOXC1 as described above is also provided.

Abstract: In one embodiment, a method of theranostic classification of a breast cancer tumor is provided, comprising obtaining a breast cancer tumor sample from a subject, detecting an expression level of FOXC1, comparing the expression level of FOXC1 to a predetermined cutoff level, and classifying the breast cancer tumor sample as belonging to a theranostic basal-like breast cancer tumor subtype or a theranostic hybrid basal-like breast cancer tumor subtype when the expression level of FOXC1 is higher than the predetermined cutoff level. In other embodiments, methods for predicting a prognosis of a basal-like breast cancer and methods of treating a basal-like breast cancer are provided.

Abstract: In one embodiment, an isolated antibody or functional fragment thereof which binds an antigenic peptide sequence of human FOXC1 is provided herein. Such antibodies or functional fragments may be used to diagnose, prognose or treat basal-like breast cancer. The antibody or functional fragment may be a monoclonal antibody produced by a hybridoma cell line. Thus, a hybridoma cell line that produces a FOXC1 monoclonal antibody which binds an antigenic peptide sequence of human FOXC1 as described above is also provided.

Abstract: In one embodiment, a method of theranostic classification of a breast cancer tumor is provided, comprising obtaining a breast cancer tumor sample from a subject, detecting an expression level of FOXC1, comparing the expression level of FOXC1 to a predetermined cutoff level, and classifying the breast cancer tumor sample as belonging to a theranostic basal-like breast cancer tumor subtype or a theranostic hybrid basal-like breast cancer tumor subtype when the expression level of FOXC1 is higher than the predetermined cutoff level.