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      One-Click Submission System Now Available for SO Preprints, learn more on how this works in our blog post and don't forget to check the video, too!

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      Precision Oncology, Signaling Pathways Reprogramming and Targeted Therapy: A Holistic Approach to Molecular Cancer Therapeutics

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      Author(s):   1 ,
      Publication date (Electronic preprint):
      Journal: ScienceOpen Preprints
      Publisher: ScienceOpen
      Keywords: Gene Mutation, Cancer Genomics, p53, K-Ras, Myc, Bcl-2, Cancer Stem Cells, Targeted Therapy, Immunotherapy, Precision Medicine
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            Revision notes 

            The title and abstract have been revised.Sections 1, 5, 6 and 7 of the article have been lightly revised and updated.Additional information and associated data submitted to the Mendeley Data, with its availability noted with citation inside the manyscript.References added to the related section based on changes made to the manuscript.

            Author Summary

            Summary

            The TCGA Research Network started in 2005 has profiled and analyzed a large number of human tumors to discover molecular aberrations at the DNA, RNA, protein, and epigenetic levels and thereby provided reliable diagnostic and prognostic biomarkers for different cancer types since then.The presence of mutated genes is strongly correlated with cancer incidence, very specific causative genes or a small set of genes for most cancers have not been confirmed after decades of genomic studies. Nobel laureate James D. Watson opined at Cancer World 2013: "We can go ahead and sequence every piece of DNA that has ever existed, but I don't think we'll find the Achilles heel of cancer. Importantly,, it is not only necessary to associate genetic mutations with different cancers but also to work on the mechanism of action of mutagens by focusing on enzymes which could invariably mediate oncogenic transformations. For example, overexpression of the ribonucleotide reductase (RnR) enzyme which catalyzes the formation of deoxyribonucleotides from ribonucleotides necessary for cell division, is implicated in many forms of cancer and the genes for the components of the enzyme are often mutated, leading to hyperactivity of the enzyme. But there are instances indicating that cytoplasmic material rather than the karyoplast would be responsible for cellular transformation that might be better explained as a consequence of certain epigenetic modulation than purely genetic changes. .RnR active site inhibitors have been developed accordingly to biophysically deactivate the enzyme when necessary, with positive results A comprehensive analysis of tumors based on their genomic studies must reveal the alterations in signaling pathways indicating patterns of vulnerabilities and the means to identify prospective targets for the development of personalized treatments and new combination therapies. In this regard, the Cancer Cell Map Initiative (CCMI), launched in 2015 by researchers at the University of California, San Francisco and the University of California, San Diego, allowed researchers to determine how hundreds of genetic mutations involved in a few types of cancer affect the activity of certain crucial proteins which ultimately lead to the manifestation of cancer. As there is a large amount of sequence data from many different cancer types, efforts are being made to extract mechanistic insights from the available information, requiring an integrated computational and experimental strategy that will help place these alterations in the higher order contexts of signaling mechanisms in cancer cells. This is the defined goal of the CCMI and has the potential to create a resource that can be used for cancer genome interpretation, enabling the identification of key complexes and pathways to better understand the biology underlying different cancer types and conditions for precise treatment of the disease,

            Abstract

            Cancer is a fatal genetic disease with different aspects of complexity, including cancer immune evasion, treatment resistance and recurrence, requiring optimized treatment for proper cure. Molecular studies have revealed that tumors are extremely heterogeneous in nature, leading to the complexity of cancer progression that is ultimately linked to its genetic machinery. It is important to note that patients with the same types of cancer respond differently to cancer treatments, indicating the need for treatment options specific to each patient. Thus, in-depth genomic study of patient’s tumor will be needed to fully understand the determinants of cancer initiation and progression for effective targeted therapy. Precision oncology has evolved as a form of cancer therapy focused on genetic profiling of tumors to identify molecular alterations involved in cancer manifestation for tailored individualized treatment of the disease. There has been a deluge of formulation and mass production of anticancer agents in recent years, mainly due to advances in genomic technologies enabling precise targeting of oncogenic pathways involved in disease. This article aims to briefly explain the foundations and frontiers of precision oncology in the context of advancements in the tools and techniques exploited in the process in order to assess its scope and importance to realize the intended goals.

            Content

            Author and article information

            Journal
            Title: ScienceOpen Preprints
            Publisher: ScienceOpen
            Publication date (Electronic preprint): 7 July 2024
            Affiliations
            [1 ] Vellore Institute of Technology, Vellore, Tamil Nadu, India ( https://ror.org/00qzypv28)
            Author notes
            Author information
            https://orcid.org/0000-0002-6021-7063
            Article
            DOI: 10.14293/PR2199.000553.v2
            SO-VID: 2776ab30-edc3-4f74-88c6-1215f2134a7f
            License:

            This work has been published open access under Creative Commons Attribution License CC BY 4.0 , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Conditions, terms of use and publishing policy can be found at www.scienceopen.com .

            History
            Date received : 15 December 2023
            Categories

            Data availability: The datasets generated during and/or analysed during the current study are available in the repository: https://data.mendeley.com/datasets/j33xfgvyyz/1
            ScienceOpen disciplines: Life sciences
            Keywords: Gene Mutation,Cancer Genomics,p53,K-Ras,Myc,Bcl-2,Cancer Stem Cells,Targeted Therapy,Immunotherapy,Precision Medicine

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