Abstract: The present invention relates to methods and compositions for inhibiting growth and proliferation of cancer cells resistant to PI3K inhibition using a combination of PDK1, SGK1 and PI3K inhibitors. The present invention is also directed to methods of treating cancer in a subject exhibiting cancer cells resistant to PI3K inhibition, comprising administering inhibitors of PI3K in combination with inhibitors of PDK1 and/or SGK1 to the subject.

Abstract: The development of a new, targeted drug delivery paradigm coupled to improved PI3K inhibitors (e.g., PI3K? inhibitors) represents a significant advance in cancer therapy. Provided herein are compounds, such as compounds of Formula (I) and (II), and pharmaceutically acceptable salts, hydrates, solvates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The compounds provided herein are PI3K (e.g., PI3K?) inhibitors and are therefore useful for the treatment and/or prevention of various diseases (e.g., proliferative diseases such as cancer). Also provided herein are nanoparticles and nanogels (e.g., P-selectin targeting nanoparticles) comprising PI3K inhibitors, such a compound described herein. In certain embodiments, a nanoparticle or nanogel described herein encapsulates a compound described herein for targeting delivery to cancer cells or tumors.

Abstract: The present disclosure provides methods for determining whether a patient diagnosed with lung cancer will benefit from or is predicted to be responsive to treatment with a therapeutic agent that targets HER2. These methods are based on detecting elevated levels of HER2 dimerization in a biological sample obtained from a lung cancer patient. Kits for use in practicing the methods are also provided.

Abstract: The present disclosure relates to methods for determining the responsiveness of a cancer to a PI3K inhibitor and kits relating thereof. The present disclosure also relates to methods for treating a subject having a cancer, where the cancer has been determined to be responsive to a PI3K inhibitor. In particular, the present disclosure provides combinations of two or more PI3KCA mutations as biomarkers for determining the responsiveness of a cancer cell to a PI3K inhibitor.

Abstract: Improved methods for treating lung cancer are provided. Tumor samples from patients are analyzed (i) by DNA sequencing to detect the presence of HER2 mutations and (ii) by mass spectrometric proteomic analysis to determine whether HER2 protein is expressed in the tumor cells. Patients respond to therapy with trastuzumab emtansine (T-DM1) or an equivalent antibody-drug conjugate when unique HER2 protein fragments are detected in the patient's tumor cells that harbor HER2 mutations. Conversely, patients do not respond to T-DM1 therapy when the tumor cells contain HER2 mutations but the unique protein fragments are not detected. Detection of HER3 in the tumor cells is a positive predictor of response to treatment.

Abstract: The present invention relates to methods and compositions for inhibiting growth and proliferation of cancer cells resistant to PI3K inhibition using a combination of PDK1, SGK1 and PI3K inhibitors. The present invention is also directed to methods of treating cancer in a subject exhibiting cancer cells resistant to PI3K inhibition, comprising administering inhibitors of PI3K in combination with inhibitors of PDK1 and/or SGK1 to the subject.

Abstract: The invention provides combinations comprising GDC-0068 or GDC-0941, or a pharmaceutically acceptable salt thereof and ME-HD7945A. The combinations are particularly useful for treating hyperproliferative disorders, such as cancer (e.g., triple negative breast cancer).

Abstract: The invention provides combinations comprising GDC-0068 or GDC-0941, or a pharmaceutically acceptable salt thereof and ME-HD7945A. The combinations are particularly useful for treating hyperproliferative disorders, such as cancer (e.g., triple negative breast cancer).