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Rewiring Oncogenic Signaling to Ther...

Zou, Xinzhi.

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Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer./
Author:	Zou, Xinzhi.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
Description:	92 p.
Notes:	Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
Contained By:	Dissertations Abstracts International85-11B.
Subject:	Infections. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31049657
ISBN:	9798382639048

Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer.
Zou, Xinzhi.

Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 92 p.

Source: Dissertations Abstracts International, Volume: 85-11, Section: B.

Thesis (Ph.D.)--Stanford University, 2023.

Despite recent advances in cancer treatments, improvements to long-term survival in metastatic solid tumors, such as pancreatic or ovarian cancer, remain limited. Current medical therapies suppress growth-promoting biochemical signals or activate immune responses to tumor-associated antigens (TAAs). However, these approaches are limited by toxicity to normal cells that utilize the same signaling pathways or express the same antigens. Previously we developed a method for Rewiring Aberrant Signaling to Effector Release (RASER) to selectively redirect hyperactive ErbB signaling, found in many solid tumors but not normal tissues, to programmable responses. Here in my thesis, I report the engineering of viral vectors that express and are regulated by RASER, resulting in the selective ablation of cancer cells exhibiting hyperactive ErbB signaling. In mice, RASER-restricted vesicular stomatitis virus (VSV) exhibited 10000-fold less toxicity per dose than parental VSV, and 10-fold less than the attenuated VSV-∆M51 variant. RASER-restricted VSV conferred a larger survival benefit in non-immune mouse models of peritoneally disseminated ErbB-hyperactive pancreatic and ovarian cancers. Thus, RASER-restricted viral activation may represent a new approach for treating ErbB-hyperactive metastatic cancers that is independent of adaptive immunity. I also successfully extended the RASER concept to additional signals caused by oncogene mutations including hyperactive c-Met and KRAS and successfully developed Ad and VSV controlled by c-Met and KRAS RASER. With its generalizability and application in vivo,RASER controlled viruses will thus build a completely new type of cancer therapy, in which synthetic proteins are engineered to specifically identify and destroy cancer cells.

ISBN: 9798382639048Subjects--Topical Terms:

1621997
Infections.

Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer.
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