Targeting Clonal Mutations with Synthetic Microbes

Michael Renteln

doi:10.20944/preprints202308.1536.v11

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preprints.org > medicine and pharmacology > oncology and oncogenics > doi: 10.20944/preprints202308.1536.v11

Preprint Review Version 11 Preserved in Portico This version is not peer-reviewed

Targeting Clonal Mutations with Synthetic Microbes

Michael Renteln

Version 1 : Received: 21 August 2023 / Approved: 21 August 2023 / Online: 22 August 2023 (07:58:07 CEST)
Version 2 : Received: 5 September 2023 / Approved: 6 September 2023 / Online: 7 September 2023 (02:54:00 CEST)
Version 3 : Received: 31 December 2023 / Approved: 2 January 2024 / Online: 2 January 2024 (10:00:17 CET)
Version 4 : Received: 4 February 2024 / Approved: 5 February 2024 / Online: 5 February 2024 (13:52:59 CET)
Version 5 : Received: 21 March 2024 / Approved: 22 March 2024 / Online: 22 March 2024 (12:06:13 CET)
Version 6 : Received: 9 May 2024 / Approved: 9 May 2024 / Online: 9 May 2024 (10:33:03 CEST)
Version 7 : Received: 7 June 2024 / Approved: 7 June 2024 / Online: 7 June 2024 (14:31:49 CEST)
Version 8 : Received: 26 June 2024 / Approved: 27 June 2024 / Online: 1 July 2024 (09:27:29 CEST)
Version 9 : Received: 5 August 2024 / Approved: 6 August 2024 / Online: 7 August 2024 (09:30:23 CEST)
Version 10 : Received: 21 August 2024 / Approved: 23 August 2024 / Online: 23 August 2024 (17:11:16 CEST)
Version 11 : Received: 10 September 2024 / Approved: 10 September 2024 / Online: 11 September 2024 (10:24:21 CEST)

How to cite: Renteln, M. Targeting Clonal Mutations with Synthetic Microbes. Preprints 2023, 2023081536. https://doi.org/10.20944/preprints202308.1536.v11 Renteln, M. Targeting Clonal Mutations with Synthetic Microbes. Preprints 2023, 2023081536. https://doi.org/10.20944/preprints202308.1536.v11

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MDPI and ACS Style

Renteln, M. Targeting Clonal Mutations with Synthetic Microbes. Preprints 2023, 2023081536. https://doi.org/10.20944/preprints202308.1536.v11

APA Style

Renteln, M. (2024). Targeting Clonal Mutations with Synthetic Microbes. Preprints. https://doi.org/10.20944/preprints202308.1536.v11

Chicago/Turabian Style

Renteln, M. 2024 "Targeting Clonal Mutations with Synthetic Microbes" Preprints. https://doi.org/10.20944/preprints202308.1536.v11

Abstract

Recently concluded, large-scale cancer genomics studies involving multiregion sequencing of primary tumors and paired metastases appear to indicate that most patients have one or more “clonal" mutations in their tumors. Clonal mutations are those that are present in all of a patient’s cancer cells. Clonally mutated proteins can potentially be targeted by inhibitors or E3 ligase glues, but developing new small molecule drugs for each patient is not feasible currently. One company is using an immunotherapy approach to specifically target clonal mutations. Another is using a different immunotherapy tactic that targets clonal and subclonal mutations. A third is planning to use a self-amplifying mRNA-based vaccination approach to target clonal mutations. To address the potential limitations of immunotherapy, I have devised another approach for exploiting clonal mutations, which I call “Oncolytic Vector Efficient Replication Contingent on Omnipresent Mutation Engagement” (OVERCOME). The ideal version of OVERCOME would employ a bioengineered facultative intracellular bacterium. The bacterium would initially be attenuated, but (transiently) reverse its attenuation upon clonal mutation detection.

Keywords

multiregion sequencing; multisample sequencing; cell-free circulating tumor DNA; clonal mutations; Achilles therapeutics; OVERCOME

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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