H. Lee Moffitt Cancer Center and Research Institute, Inc.

University of Central Florida Research Foundation, Inc.

Nupam Mahajan

Kiran N Mahajan

Nicholas James Lawrence

Harshani Lawrence

Domenico Coppola

Ratna Chakrabarti

Richard Ottman

Disclosed is a method for selecting a cancer therapeutic for a patient that involves assaying a tumor biopsy sample from the subject to detect PAXIP1 expression, and selecting a WEE1 inhibitor as the cancer therapeutic if PAXIP1 is detected in the tumor biopsy sample.

Allosteric inhibitor of WEE1 kinase

A biomarker is disclosed that can distinguish aggressive epithelial tumors in a tissue biopsy from, for example, normal, hyperplastic, and benign neoplastic tumors. The biomarker can also identify epithelial tumors that have become resistant to hormone therapy. Therefore, methods are disclosed for providing diagnosis and prognosis of a subject having, or suspected of having, an epithelial tumor, such as a prostate tumor.

Methods for diagnosis and prognosis of epithelial tumors

Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of ACK1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new ACK1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I are disclosed.

Inhibitors of ACK1/TNK2 tyrosine kinase

Described are cancer therapies and anti-cancer compounds. In particular, disclosed are inhibitors of Ack1 tyrosine kinase and their use in the treatment of cancer. Methods of screening for new Ack1 tyrosine kinase inhibitors are also disclosed. In specific example, compound having Formula I through IV are disclosed.

Phosphorylation of histones was observed at certain tyrosine residues which have not been associated with epigenetic modification. These sites include H2B Tyr37, H4 Tyr88 and Tyr 51 and H3 Tyr99. Kinases responsible for the phosphorylation as well as downstream genes regulated by such phosphorylation were also identified. Antibodies that are specific to such phosphorylated histones have been generated, which are useful for detecting the phosphorylation and related events. With such findings, the present disclosure provides compositions and methods for disease diagnosis, prognosis and therapy selection, in particular for cancer, obesity and diabetes.

Phosphorylation of histones and uses thereof

AKT/PKB kinase is a key signaling component of one of the most frequently activated pathways in cancer and is a major target of cancer drug development. The present study uncovered that growth factors binding to RTKs lead to activation of a non-receptor tyrosine kinase, Ack1 (TNK2), which directly phosphorylates AKT at a conserved tyrosine 176 residue. Tyr176-phosphorylated AKT binds to phosphatidic acid and localizes to the plasma membrane, leading to AKT activation. Expression levels of Tyr176-phosphorylated-AKT and Tyr284-phosphorylated-Ack1 were positively correlated with the severity of disease progression, and inversely correlated with the survival of breast, prostate, lung and pancreatic cancer patients.

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Tampa, FL, United States of America

Nupam Mahajan