University of California

Intellikine LLC

Davide Ruggero

Peter Carroll

Hao Nguyen

Crystal Conn

Yi Liu

Pingda Ren

Liansheng Li

Troy Edward Wilson

Kevan M Shokat

Katrina Chan

Andrew Gaheem Hsieh

Christian Rommel

Beth Apsel

David Pearce

Matthew Janes

John Thomas Cunningham

David Fruman

Morris Feldman

Steve Worland

Merritt Edlind

James Appleman

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.

The present invention provides methods of selectively killing a cell, comprising contacting the cell with an agent that inhibits phospho-ribosyl pyrophophosphate synthetase 2 (PRPS2). The present invention also provides methods of identifying a candidate agent that selectively kills neoplastic cells that are Myc-hyperactivated via inhibition of PRPS2.

Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) as a therapeutic target in cancer treatment

The present invention provides methods and compositions for selective modulation of certain protein kinases, and especially mTor complexes. The methods and compositions are particularly useful in inhibiting mTor selectively for therapeutic applications.

MTOR modulators and uses thereof

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San Francisco, CA, United States of America

Davide Ruggero