國立虎尾科技大學 |

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

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer./
Author:	Zou, Xinzhi.
Description:	1 online resource (92 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
Contained By:	Dissertations Abstracts International85-11B.
Subject:	Infections. -
Online resource:	click for full text (PQDT)
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. - 1 online resource (92 pages)

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

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

Includes bibliographical references

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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798382639048Subjects--Topical Terms:

882242
Infections.
Index Terms--Genre/Form:

554714
Electronic books.

Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer.
LDR:03182ntm a22004097 4500 001 1152649
005 20241209114621.5
006 m o d
007 cr mn ---uuuuu
008 250605s2023 xx obm 000 0 eng d
020 $a 9798382639048
035 $a (MiAaPQ)AAI31049657
035 $a (MiAaPQ)STANFORDsw016fr9351
035 $a AAI31049657
040 $a MiAaPQ $b eng $c MiAaPQ $d NTU
100 1 $a Zou, Xinzhi. $3 1479702
245 1 0 $a Rewiring Oncogenic Signaling to Therapeutic Viral Activation for Treatment of Metastatic Cancer.
264 0 $c 2023
300 $a 1 online resource (92 pages)
336 $a text $b txt $2 rdacontent
337 $a computer $b c $2 rdamedia
338 $a online resource $b cr $2 rdacarrier
500 $a Source: Dissertations Abstracts International, Volume: 85-11, Section: B.
500 $a Advisor: Lin, Michael;Qi, Stanley;Wang, Bo.
502 $a Thesis (Ph.D.)--Stanford University, 2023.
504 $a Includes bibliographical references
520 $a 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.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2024
538 $a Mode of access: World Wide Web
650 4 $a Infections. $3 882242
650 4 $a Ovarian cancer. $3 1479703
650 4 $a Plasma. $3 1045777
650 4 $a Pancreatic cancer. $3 1479704
650 4 $a Medical prognosis. $3 1471053
650 4 $a Metastasis. $3 673770
650 4 $a Toxicity. $3 1413674
650 4 $a Reagents. $3 1372660
650 4 $a Hyperactivity. $3 1469557
650 4 $a Cytotoxicity. $3 1465447
650 4 $a Cancer therapies. $3 1468563
650 4 $a Viruses. $3 579004
650 4 $a Genomes. $3 600075
650 4 $a Vectors (Biology). $3 1479705
650 4 $a Reproducibility. $3 1471787
650 4 $a Cell culture. $3 583545
650 4 $a Breast cancer. $3 1413554
650 4 $a Behavioral psychology. $3 1179418
650 4 $a Biology. $3 599573
650 4 $a Cellular biology. $3 1148666
650 4 $a Genetics. $3 578972
650 4 $a Medicine. $3 644133
650 4 $a Oncology. $3 593951
650 4 $a Pharmaceutical sciences. $3 1180569
650 4 $a Toxicology. $3 580973
655 7 $a Electronic books. $2 local $3 554714
690 $a 0384
690 $a 0306
690 $a 0379
690 $a 0369
690 $a 0564
690 $a 0992
690 $a 0572
690 $a 0383
710 2 $a ProQuest Information and Learning Co. $3 1178819
710 2 $a Stanford University. $3 1184533
773 0 $t Dissertations Abstracts International $g 85-11B.
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=31049657 $z click for full text (PQDT)