University of California

Peter Carroll

Tom F Lue

Yuet W Kan

Ching-Shwun Lin

Davide Ruggero

Hao Nguyen

Crystal Conn

Pamela Paris

Matthew Cooperberg

In cancers such as prostate cancer, the combination of PTEN loss and activation of Myc activates an adaptive stress response that enables tumor cells to escape the stress of massively upregulated protein synthesis. This pro-survival response is mediated by the PERK-phosphorylated eIF2α axis of the UPR adaptive response. Agents that disrupt PERK-eIF2α pathways disrupt the adaptive response and lead to cancer cell death from uncontrolled growth. For example, ISRIB and derivatives may be employed as therapeutic agents to disrupt PERK-mediated adaptive mechanisms. Additionally PTEN loss and activation of Myc provides a diagnostic marker that enables better prognosis and the selection of amenable treatments.

Cancer treatment targeted to tumor adaptive responses to protein synthesis stress

In cancers such as prostate cancer, the combination of PTEN loss and activation of Myc activates an adaptive stress response that enables tumor cells to escape the stress of massively upregulated protein synthesis. This pro-survival response is mediated by the PERK-phosphorylated eIF2&#x3b1; axis of the UPR adaptive response. Agents that disrupt PERK-eIF2&#x3b1; pathways disrupt the adaptive response and lead to cancer cell death from uncontrolled growth. For example, ISRIB and derivatives may be employed as therapeutic agents to disrupt PERK-mediated adaptive mechanisms. Additionally PTEN loss and activation of Myc provides a diagnostic marker that enables better prognosis and the selection of amenable treatments.

This disclosure relates to methods, computer products, computer-implemented methods, and systems for predicting the probability or risk of prostate cancer recurrence and tumor aggressiveness in a patient. The method is based, in part, on the patient's risk profile that includes the presence/degree of specific copy number variations and predictive clinical factors. The methods and systems can be used to aid in treatment selection.

Determining risk of prostate tumor aggressiveness

The invention provides a method for preventing or treating male erectile dysfunction or female sexual arousal disorder by administering an effective amount of one or more factors from a group of factors including vascular endothelial growth factor, brain-derived neurotrophic factor, basic fibroblast growth factor, neurotrophin-3, neurotrophin-4, or angiopoietin-1, wherein the factor is a full length protein or a nucleic acid encoding the factor, or a functional derivative or fragment thereof, or an agent that enhances production and/or male erection or female sexual arousal stimulating function of the factor(s). Combinations, kits, and combinatorial methods are also provided.

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San Francisco, CA, United States of America

Peter Carroll