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

University of South Florida

Douglas C Marchion

Johnathan M Lancaster

Dung-Tsa Chen

Yin Xiong

The present invention relates to the BAD pathway's influence on development, progression, chemo-sensitivity, and overall survival for multiple human cancers and its potential as a therapeutic target to increase chemo-sensitivity. BAD pathway expression was associated with the development and/or progression of breast, colon, and endometrial cancers, relapse-free survival from breast cancer, and overall survival from ovarian, colon, and brain cancers. Expression was also associated with in vitro sensitivity to a range of cytotoxic agents. pBAD levels were higher in cancer versus immortalized normal cells and chemo-resistant versus&#x2014;sensitive cancer cells and associated with increased cell proliferation.

Method of diagnosing, treating and determining progression and survival of cancer cells using BCL-2 antagonist of cell death (BAD) pathway gene signature

Biomarkers, methods, assays, and kits are provided for determining the prognosis of and treating a patient with ovarian cancer. Also disclosed are biomarkers, methods, assays, and kits for predicting the sensitivity of ovarian cancer cells to chemotherapy.

O-glycan pathway ovarian cancer signature

Despite initial sensitivity BAD-protein phosphorylation were evaluated in patient samples and cell lines as determinants of chemo-sensitivity and/or clinical outcome, and as therapeutic targets. Induced in-vitro OVCA cisplatin-resistance was associated with BAD-pathway expression. Expression of the pathway was also associated with resistance of 7 different cancers cell-types to 8 chemotherapeutic agents. Phosphorylation of the BAD-protein was associated with platinum-resistance in OVCA cells and primary OVCA specimens, and also overall patient survival. Targeted modulation of BAD-phosphorylation levels influenced cisplatin-sensitivity. A 47-gene BAD-pathway signature was associated in-vitro phospho-BAD levels and with survival of 838 patients with ovarian, breast, colon, and brain cancer. The survival advantage associated with both BAD-phosphorylation and also the BAD-pathway signature was independent of surgical cytoreductive status. The BAD apoptosis pathway influences human cancer chemo-sensitivity and overall survival. The pathway is useful as a biomarker of therapeutic response, patient survival, and therapeutic target.

Bad phosphorylation determines ovarian cancer chemo-sensitivity and patient survival

The phosphorylation status of the BAD protein is a determinant of ovarian cancer cell responsiveness to platinum chemotherapy. Indirect manipulation of BAD phosphorylation status influences cisplatin sensitivity. BAD phosphorylation represents a biomarker that predicts platinum sensitivity and is a therapeutic target to increase platinum sensitivity. The methods employ phospho-specific antibody against a particular amino acid residue or site. Phospho-specific protein characterization methods include immunohistochemical (IHC), flow cytometric, immunofluorescent, capture-and-detection, or reversed phase assay.

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Seminole, FL, United States of America

Douglas C Marchion