Cedars-sinai Medical Center

Xiaojiang Cui

Dhruv Sareen

Lali K Medina-Kauwe

Loren A Ornelas

Beth Y Karlan

Dong-Joo Cheon

Zhenqiu Liu

Jessica Sims

Sareen Dhruv

Michael Taguaim

Chris Hanson

Sandra Orsulic

Ying Qu

Mourad Tighiouart

Armando E Giuliano

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.

In vitro induction of mammary-like differentiation from human pluripotent stem cells

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.

Generation of induced pluripotent stem cells from normal human mammary epithelial cells

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.

Molecular signatures of ovarian cancer

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. Further disclosed herein are methods of treating cancer in a patient, the method comprising identifying a patient who is resistant to anti-HER2 therapy; and administering to the patient a therapeutically effective amount of a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; and a sulfonated corrole molecule bound to the polypeptide sequence. Finally disclosed herein 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 a drug delivery molecule, comprising a polypeptide molecule adapted to target and/or penetrate a type of cell; and a sulfonated corrole molecule bound to the polypeptide sequence.

Targeting trastuzumab-resistant HER2+ breast cancer with a HER3-targeting nanoparticle

Growing community of inventors

Arcadia, CA, United States of America

Xiaojiang Cui