Targeted Cancer Therapy Has Been Defined at a Narrow Biological Level—A Hierarchical and Semi-Quantitative Reassessment of Genomic, Redox, and Metabolic Targeting

“Targeted cancer therapy” is commonly operationalized as mutation-matched pharmacologic therapy. These therapies represent genuine scientific advances. However, population-level analyses indicate that eligibility for genome-targeted drugs remains in the low-teens percentage range, with estimated durable benefit affecting only a small single-digit fraction of metastatic patients once intratumoral heterogeneity (ITH) and evolutionary resistance are considered[1–4].Cancer is not solely a genomic disease; genomic alterations arise and operate within a broader systems-level biological context. Tumor survival and evolutionary persistence depend on distributed metabolic and redox programs—including redox fragility[5] and metabolic inflexibility[6]—that transcend individual mutations and span diverse tumor types and tumor cell populations. Because these programs reflect functional survival infrastructure rather than rare mutational events, they represent broader and potentially more universally exploitable therapeutic targets.This paper argues that oncology has, at times, conflated molecular precision with systemic comprehensiveness. We introduce a dual-axis evaluative framework distinguishing Specificity of Target from Distribution of Vulnerability, and propose a hierarchical model of cancer targeting encompassing:1. Genomic targeting (mutation-specific drugs)2. Redox targeting (pharmacologic ascorbate / high-dose intravenous vitamin C; HDIVC)[7–10]3. Metabolic/systemic targeting (ketogenic metabolic therapy; insulin–IGF modulation)[11–14]Using published eligibility data, ITH metrics, peroxide detoxification studies, and pan-cancer metabolic stratification analyses, we construct a semi-quantitative comparison of “Targetable Fraction” and “Effective Target Coverage” across these layers. We demonstrate that genomic targeting is highly specific but structurally narrow, whereas redox and metabolic targeting operate at broader biological levels with wider theoretical distribution. Importantly, these layers are complementary rather than mutually exclusive, and a systems-oncology doctrine should evaluate their combined role in expanding effective target coverage.This manuscript expands the conceptual taxonomy of targeted cancer therapy and establishes a formal record that redox and metabolic interventions constitute biologically coherent targeting modalities within a layered oncology framework.