Dana-Farber-Cancer Institute Inc.

Novartis Ag

Harvard College

Jean Zhao

Yubao Wang

Nathanael Schiander Gray

Tinghu Zhang

Thomas M Roberts

Hwan Geun Choi

Hai-Tsang Huang

Gordon James Freeman

Jeffrey Charles Way

Jing Ni

Nathanael S Gray

William C Hahn

Xizhong Huang

Fleur M Ferguson

Avram Lev Robinson-Mosher

David E Hill

Jesse S Boehm

John Blenis

Junxia Min

Haoxuan Tong

Ben B Li

Xin Cheng

Yunneng Tang

Shaozhen Xie

Johann Bergholz

The present invention is based, in part, on cancer vaccine compositions that comprise PTEN- and p53-deficient cancer cells with activated TGFβ-Smad/p63 signaling pathway, and methods for using same to prevent and/or treat cancer.

Cancer vaccine compositions and methods for using same to prevent and/or treat cancer

The present invention is based, in part, on the identification of novel FI.3K-mTORCI-S6K 1 signaling pathway biomarkers predictive of responsiveness to anti-cancer therapies.

P13K-MTORC1-S6K1 signaling pathway biomarkers predictive of anti-cancer responses

The present invention relates to methods of treating brain metastases using synergistic combinations of anti-PI3K and anti-mTOR therapies. It has also been determined that blocking PI3K and mTOR provides therapeutic benefit for treating brain metastases.

Methods for treating brain metastases using combinations of anti-P13K and anti-mTOR agents

The present invention provides methods for measuring translation rates of RNA associated with a ribosome (e.g., mRNA) in a rapid, cost-effective, and targeted manner.

Methods for measuring RNA translation rates

The present invention relates to use of pyrimido-diazepinone compounds that are able to modulate protein kinases such as PI3K-&#x3b3; and PI3K-&#x3b4;, which are members of the Class I Type IA and Class I Type IB family of phosphatidylinositol-4,5-bisphosphate 3-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.

Pyrimido-diazepinone kinase scaffold compounds and methods for treating PI3K-mediated disorders

The present invention relates to methods for treating PTEN deficient epithelial cancers using a combination of anti-PI3Kbeta and anti-immune checkpoint agents.

Methods for treating PTEN deficient epithelial cancers using a combination of anti-PI3KBETA and anti-immune checkpoint agents

Provided herein are small molecule inhibitors of maternal embryonic leucine zipper kinase (MELK) having the structure of formula (I), wherein X and R-Rare defined in the specification. The compounds are useful for treating cancer and other conditions or diseases associated with aberrant MELK expression. Also provided herein are pharmaceutical compositions comprising a compound of formula (I) and a pharmaceutically acceptable carrier. The invention also provides methods of treating cancers associated with over-expression of MELK.

Salicylate inhibitors of MELK and methods of use

Provided herein are tricyclic small molecule inhibitors of maternal embryonic leucine zipper kinase (MELK). The compounds are useful for treating cancer and other conditions or diseases associated with aberrant MELK expression. Also provided herein are pharmaceutical compositions comprising a tricyclic compound of the invention and a pharmaceutically acceptable carrier. The invention also provides methods of treating cancers associated with over-expression of MELK.

Tricyclic kinase inhibitors of MELK and methods of use

The methods of the present invention, relate to the surprising determination that the level of phosphorylation of position 406 (e.g., a serine residue) of human eukaryotic initiation factor 4B (eIF4B), or a corresponding phosphorylatable amino acid of an ortholog thereof, serves as a biomarker for MELK enzymatic (e.g., kinase) and/or oncogenic activity. The methods of the present invention further relate to the surprising determination that the level of phosphorylation of position 3 (e.g., a threonine residue) and/or position 10 (e.g., a serine residue) and/or position 11 (e.g., a threonine residue) of human Histone M3, or a corresponding phosphorylatable amino acid of an ortholog thereof, also serves as a biomarker for MELK enzymatic (e.g., kinase) and/or oncogenic activity.

Biomarker for MELK activity and methods of using same

Methods for inhibiting growth or proliferation of breast cancer cells are provided. The methods include administering to a subject in need thereof in an amount that is effective to inhibit growth or proliferation of the breast cancer cells a MELK inhibitor, wherein the breast cancer cells are estrogen receptor (ER) negative. In some aspects, the methods include administering to a subject in need thereof in an amount that is effective to inhibit growth or proliferation of the breast cancer cells a MELK inhibitor, a FoxM1 inhibitor or a MELK inhibitor and a FoxM1 inhibitor, wherein the breast cancer cells are estrogen receptor (ER) negative. Methods of treatment for breast cancer and methods of identifying patients having cancer that are likely to benefit from treatment with a MELK inhibitor, a FoxM1 inhibitor or a MELK inhibitor and a FoxM1 inhibitor are also provided.

MELK regulation for the treatment of breast cancer

Provided herein are nucleic acids, proteins, vectors, cells, kits, devices and methods useful for identifying regulatable proteins that are able to complement components of cellular signaling pathways. Also provided are compositions and methods using these complementing genes directly as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics. Further provided are methods for using changes caused by expression of the complementing genes to indirectly identify associated genes to be used as markers for cancer diagnosis or prognosis and as targets for anti-neoplastic therapeutics.

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Brookline, MA, United States of America

Jean Zhao