Beyond mutation burden: biological termination as a systems perspective on cancer.
- 1Clinic of Medical Oncology, MHAT "Nadezhda", Sofia, Bulgaria.
- 2Hospital Pharmacy, MHAT "Nadezhda", Sofia, Bulgaria.
- 3Department of Propedeutics of Internal Diseases, UMHAT "St. Marina", Varna, Bulgaria.
Abstract
Cancer is traditionally viewed as a genetic disease driven by the accumulation of mutations that disrupt normal cellular regulation. While this framework has generated profound biological insights, several observations remain incompletely explained, including the presence of driver mutations in normal tissues, the occurrence of highly aggressive tumors with low mutational burdens, and the convergence of genetically diverse cancers toward similar phenotypic states. This article proposes that malignant transformation may be understood as a progressive failure of biological termination mechanisms responsible for constraining developmental, proliferative, and adaptive cellular programs. Drawing upon concepts from information theory, systems biology, developmental biology, and regulatory network dynamics, cancer is interpreted as a persistent pathological state in which biological processes that would normally terminate remain active beyond their physiological context. This framework generates several testable predictions, including the emergence of aggressive tumors despite limited mutational complexity, convergence of distinct genetic alterations upon common regulatory attractors, and the potential prognostic value of measures of informational and regulatory disorganization. Together, these observations suggest that malignant behavior may depend not only on genetic alterations themselves but also on the organizational states through which biological information is interpreted and executed.
Related
- Distribution, diversity, and biological risk of henipavirus from a One Health perspective: A mini-review
- Radiogenomic modeling of EGFR mutation status in brain metastases from lung adenocarcinoma: a multicenter study with biological interpretability
- Primary Bone Vascular Neoplasms: An Integrated Biological Perspective from Bone Pathology to Precision Oncology
- A Clinical Perspective on Multidimensional Assessment of Clinical High-Risk States for Psychosis Beyond Transition Prediction
- Molecular Fingerprinting Enables Mass Quantification and Semi-Quantitative Source Apportionment of Black Carbon in Biological Samples and Beyond
BibTeX
@article{donev2026beyond,
title = {{Beyond mutation burden: biological termination as a systems perspective on cancer.}},
author = {Ivan Shterev Donev and Mila Petrova Petrova and Mariyana Ilieva Eneva and Yavor Kostadinov Kashlov and Sonya Draganova},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1942325},
url = {https://europepmc.org/article/MED/42948173},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beyond mutation burden: biological termination as a systems perspective on cancer.
AU - Ivan Shterev Donev
AU - Mila Petrova Petrova
AU - Mariyana Ilieva Eneva
AU - Yavor Kostadinov Kashlov
AU - Sonya Draganova
PY - 2026
DA - 2026/10/13
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1942325
UR - https://europepmc.org/article/MED/42948173
AB - Cancer is traditionally viewed as a genetic disease driven by the accumulation of mutations that disrupt normal cellular regulation. While this framework has generated profound biological insights, several observations remain incompletely explained, including the presence of driver mutations in normal tissues, the occurrence of highly aggressive tumors with low mutational burdens, and the convergence of genetically diverse cancers toward similar phenotypic states. This article proposes that malignant transformation may be understood as a progressive failure of biological termination mechanisms responsible for constraining developmental, proliferative, and adaptive cellular programs. Drawing upon concepts from information theory, systems biology, developmental biology, and regulatory network dynamics, cancer is interpreted as a persistent pathological state in which biological processes that would normally terminate remain active beyond their physiological context. This framework generates several testable predictions, including the emergence of aggressive tumors despite limited mutational complexity, convergence of distinct genetic alterations upon common regulatory attractors, and the potential prognostic value of measures of informational and regulatory disorganization. Together, these observations suggest that malignant behavior may depend not only on genetic alterations themselves but also on the organizational states through which biological information is interpreted and executed.
SN - 2296-634X
ER -