Advanced Molecular Solutions for Cancer Therapy—The Good, the Bad, and the Ugly of the Biomarker Paradigm

Iacobas, Dumitru Andrei

doi:10.3390/cimb46030109

Cited by 2 publications

(2 citation statements)

References 26 publications

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“…As argued in a recent Editorial [94], there is no real cancer gene biomarker, since almost all genes were reported as mutated or/and regulated in all types of cancer cases. There is also no fit-for-all cancer gene therapy, since not only each person, but even each clone in the same tumor has a distinct response to the manipulation of a particular gene.…”

Section: Discussionmentioning

confidence: 99%

Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways

Iacobas,

Iacobas

2024

Genes

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The genetic causes of the differentiated, highly treatable, and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully understood. The mostly accepted PTC etiology blames the altered sequence or/and expression level of certain biomarker genes. However, tumor heterogeneity and the patient’s unique set of favoring factors question the fit-for-all gene biomarkers. Publicly accessible gene expression profiles of the cancer nodule and the surrounding normal tissue from a surgically removed PTC tumor were re-analyzed to determine the cancer-induced alterations of the genomic fabrics responsible for major functional pathways. Tumor data were compared with those of standard papillary and anaplastic thyroid cancer cell lines. We found that PTC regulated numerous genes associated with DNA replication, repair, and transcription. Results further indicated that changes of the gene networking in functional pathways and the homeostatic control of transcript abundances also had major contributions to the PTC phenotype occurrence. The purpose to proliferate and invade the entire gland may explain the substantial transcriptomic differences we detected between the cells of the cancer nodule and those spread in homo-cellular cultures (where they need only to survive). In conclusion, the PTC etiology should include the complex molecular mechanisms involved in the remodeling of the genetic information processing pathways.

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Section: Discussionmentioning

confidence: 99%

Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways

Iacobas,

Iacobas

2024

Genes

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“…By providing the most theoretically possible comprehensive measure of the transcriptome alteration in cancer, the GFP approach is the alternative of choice to the biomarker paradigm [103]. However, GFP findings should be completed by better equipped laboratories through pathophysiological experiments to identify the molecular mechanisms responsible for controlling the transcripts' abundances and formation of gene networks.…”

Section: Discussionmentioning

confidence: 99%

Papillary Thyroid Cancer Remodels the Genomic Fabrics of DNA Replication, Repair and Transcription

Iacobas,

Iacobas

2024

Preprint

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The genetic causes of the differentiated, highly treatable and mostly non-fatal papillary thyroid cancer (PTC) are not yet fully known. The widely accepted PTC etiology blames altered sequence or/and expression level of certain biomarker genes. However, our previous studies found that the PTC biomarkers played significantly lower roles than the personalized PTC Gene Master Regulators. Our publicly accessible gene expression data from the cancer nodule and the surrounding normal tissue of surgically removed PTC tumor were re-analyzed to determine the transcriptomic effects on the genomic fabrics responsible for the DNA replication, repair and transcription. Tumor results were compared to the gene expression profiles of the papillary (BCPAP) and the anaplastic (8505C) human thyroid cancer cell lines. The analyses were carried out from the Genomic Fabric Paradigm (GFP) perspective that provides the most theoretically possible comprehensive characterization of the transcriptome and its alterations in disease. The study indicated that, in addition to regulating numerous genes, changes in the homeostatic control of transcript abundances and remodeling of the gene networks had major contributions to the PTC occurrence, resilience and proliferation. Therefore, the molecular mechanisms responsible for gene expression control and inter-coordination should also be considered when designing personalized anti-cancer gene therapies.

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Advanced Molecular Solutions for Cancer Therapy—The Good, the Bad, and the Ugly of the Biomarker Paradigm

Abstract: Identifying the most effective actionable molecules whose “smart” manipulation might selectively kill/slow down/stop the proliferation of cancer cells, with few side effects on the normal cells of the tissue, was for decades the single major objective of countless investigators [...]

Cited by 2 publications

References 26 publications

Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways

Papillary Thyroid Cancer Remodels the Genetic Information Processing Pathways

Papillary Thyroid Cancer Remodels the Genomic Fabrics of DNA Replication, Repair and Transcription

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