A Unified Theoretical Integrative Model on the Prenatal Origin, Metabolic Sustenance, Immune Evasion, and Spontaneous Remission of Cancer

This manuscript presents an integrative theoretical framework proposing a possible prenatal contribution to cancer susceptibility through fetal programming mechanisms associated with cortisol exposure during critical developmental windows. The model hypothesizes that elevated prenatal cortisol may interfere with terminal cellular differentiation through glucocorticoid receptor–dependent pathways, potentially generating long-lived residual cell populations that remain dormant for decades and may later be reactivated by biological, environmental, or physiological factors. The framework further explores potential interactions among prenatal stress, epigenetic programming, carcinogenic exposures, immune regulation, viral oncogenesis, and tumor initiation. The work does not claim experimental validation. Rather, it proposes a set of explicit, falsifiable hypotheses intended to stimulate discussion and future investigation across developmental biology, oncology, endocrinology, epigenetics, and translational research. A complementary methodological annex accompanies the manuscript, providing a structured classification of hypotheses, levels of evidence, validation criteria, falsification criteria, and recommended experimental approaches. The purpose of the annex is to distinguish clearly between established scientific knowledge, evidence-supported mechanisms, theoretical inferences, and original hypotheses. This work should be considered a theoretical and exploratory contribution designed to generate testable research questions rather than definitive conclusions regarding cancer etiology.