A Multidimensional Dissection of Carcinogenesis

Freedom Preetham
Meta Multiomics
Published in
4 min readMar 6, 2024


Cancer, a quintessential paradigm of pathological complexity, manifests as a consequence of multifactorial interactions that perturb the cellular and molecular equilibrium, culminating in unregulated cellular proliferation and neoplastic transformation. In this blog, I aim to dissect the multifaceted etiology of cancer.

The genesis of cancer can be explained through six principal vectors: Genetic Mutations, Epigenetic Alterations, Chromosomal Aberrations, Viral Oncogenesis, Environmental Carcinogenesis, and the Dysregulation of Intracellular Signaling Pathways and Metabolic Networks. Each vector represents a critical axis in the multidimensional space of carcinogenesis, interlinking genetic predispositions with environmental exposures and viral interactions to orchestrate the cellular derangement characteristic of cancer.

1. Genetic Mutations

The bedrock of oncogenic initiation and progression, somatic and germline mutations in proto-oncogenes and tumor suppressor genes engender aberrant cell growth and impede apoptotic cascades. The mutational landscape encompasses point mutations, insertions, deletions, and copy number variations that either activate oncogenic pathways or dismantle genomic surveillance mechanisms.

2. Epigenetic Alterations

Oncogenesis is further complicated by epigenetic dysregulation, encompassing DNA methylation, histone modification, and non-coding RNA-mediated silencing. These reversible modifications orchestrate a dysregulated gene expression profile, facilitating oncogene overexpression or the silencing of tumor suppressor genes without altering the primary DNA sequence.

3. Chromosomal Aberrations

Structural genomic rearrangements, including aneuploidies, translocations, and gene amplifications or deletions, disrupt the genomic integrity, leading to oncogene amplification or the inactivation of tumor suppressor genes. These aberrations are pivotal in oncogenic signaling pathway deregulation, promoting clonal expansion and heterogeneity.

4. Viral Oncogenesis

Oncogenic viruses, through the integration of viral genomes into host DNA, induce carcinogenesis by viral oncogene expression or by interfering with tumor suppressor gene functions. This vector elucidates the role of viral elements in modulating host cellular machinery towards a malignant phenotype.

5. Environmental Carcinogenesis and Lifestyle Factors

Extrinsic factors, including chemical carcinogens, ionizing radiation, and lifestyle-related factors (e.g., tobacco consumption, dietary constituents, physical inactivity), contribute to the mutagenic burden and inflammatory milieu conducive to cancer initiation and progression.

6. Dysregulation of Intracellular Signaling Pathways and Metabolic Networks

The aberration in signal transduction pathways that govern cell cycle progression, apoptosis, and cellular metabolism underlies oncogenesis. The Warburg effect, characterized by the preferential utilization of glycolysis over oxidative phosphorylation in cancer cells, exemplifies the metabolic reprogramming in the neoplastic milieu.


The following table presents an educated estimation of the contributions of these oncogenic vectors to cancer development:

Statistical guess on %

These estimations reflect the intricate and heterogeneous nature of cancer causation, emphasizing the interplay among genetic predispositions, environmental exposures, lifestyle choices, and cellular dysregulation across various cancer types. This quantitative framework emphasizes the necessity for a precision medicine approach in oncology, tailoring diagnostic and therapeutic strategies to the unique molecular and genetic landscapes of individual malignancies.

In our analysis, it becomes evident that a substantial 65% of cancer causation is attributable to genomic aberrations, with environmental carcinogenesis — contributing another 25% — also exerting a significant impact on genomic integrity. This emphasizes the imperative for cancer intervention strategies to pivot towards the realm of functional genomics.

Presently, a considerable portion of oncological research and therapeutic interventions is anchored in proteomics. However, as our understanding deepens, a paradigm shift is anticipated, with a more pronounced focus on upstream genomic regions. Cognit.AI, with its pioneering generative AI enabled, cross-cell, cross-species genomic platform, is at the forefront of this shift. It specializes in the high-resolution fine mapping of complex diseases like cancer within these upstream domains. By operating at the functional genomics level, Cognit facilitates the identification of pharmacodynamic biomarkers that are not only high in resolution but also actionable, marking a significant advancement in our approach to cancer research and treatment.

In sum, the landscape of cancer etiology presents an intricate web of genetic, epigenetic, environmental, and viral factors, all coalescing within the crucible of cellular metabolism and signaling networks to drive neoplastic transformation.

The elucidation of these complex interactions necessitates a concerted effort across disciplines, harnessing advanced molecular and computational tools to untangle the oncogenic nexus. As we advance our understanding of these multifarious processes, we edge closer to unraveling the Gordian knot of cancer, heralding a new era of targeted therapies and preventative strategies in oncology. This exploration invites further scholarly dialogue and collaborative inquiry, propelling the frontier of cancer research into uncharted territories of molecular understanding and therapeutic innovation.