Commentary proposes etiological tumor classification for clinical research

A commentary published in Holistic Integrative Oncology proposes a new biological classification of tumors based on integrative medicine, dividing cases into innate, acquired and combined-etiology categories. The framework is intended to connect tumor biology with inherited mutations, environmental exposures, infections, metabolic and endocrine influences, and psychological factors. Its authors describe it as a conceptual proposal with heuristic clinical value, not a validated diagnostic standard, and say that evidence-based treatment strategies for each category require further dedicated investigation.

The commentary was published in 2026 and adapts selected viewpoints from a related Chinese-language article that appeared in December 2024. The proposal addresses an inconsistency described by the authors: the same treatment regimen may produce different outcomes among people with apparently similar tumors, while different protocols may have different effects within one tumor type. Conventional classifications organize cancers by tissue of origin, including epithelial, neurogenic and mesenchymal tumors; by extent of invasion, from early-stage to late-stage disease; and by malignancy grade, from low to high.

The commentary does not dismiss these systems. Instead, it argues that they primarily characterize what a tumor is, where it arose or how far it has progressed, while leaving its underlying etiological interactions less fully represented. Under the proposed system, innate tumors are principally associated with high-penetrance hereditary mutations.

Examples include hereditary breast and ovarian cancer associated with BRCA1 or BRCA2 variants, Lynch syndrome involving colorectal and endometrial cancers, and retinoblastoma linked to RB1. These syndromes commonly show familial clustering, and carriers of relevant germline variants have a significantly greater risk of particular cancers than the general population. The authors characterize innate tumors as generally slow-growing and associated with absent or minimal metastasis, with surgery, radiotherapy, chemotherapy or combinations of these treatments often relevant to their management.

They estimate that innate tumors represent about 5% to 10% of all tumors in China, although the commentary presents this as an estimate rather than as the result of a new population-based prevalence study. Acquired tumors are described as developing under the influence of environmental, infectious, endocrine, metabolic and psychological factors rather than primarily through inherited mutations. Environmental factors discussed include smoking, alcohol consumption, exposure to dust, ionizing radiation, ultraviolet radiation, aflatoxins and nitrites.

The commentary cites research estimating that diet accounts for at least 75% of colorectal cancer risk, ultraviolet exposure for 65% to 86% of melanoma risk and approximately 90% of nonmelanoma skin cancers, while smoking and alcohol consumption account for about 75% of head and neck cancers. These population-level attributions are presented as evidence that acquired or modifiable factors contribute substantially to several cancers; they are not presented as measurements that predict an individual patient’s outcome with certainty. Repeated or long-term infections form one part of the acquired category in the proposal.

Pathogens named by the authors include Helicobacter pylori , hepatitis B virus, hepatitis C virus, human papillomavirus, cytomegalovirus and Epstein–Barr virus. The commentary describes three broad mechanisms through which infection may contribute to tumor formation: direct viral action, including integration of viral DNA or inactivation of tumor-suppressor genes; indirect induction through chronic inflammation, as described for HBV and HCV; and indirect induction through immune suppression. Viral cancers may also involve sustained expression of oncogenes that influence cell proliferation or apoptosis, while retroviruses can induce tumors through insertional mutagenesis.

Within the proposed logic, prevention and treatment of associated infections are therefore relevant considerations, but the commentary does not report an outcome study showing that its classification improves clinical results. Metabolic and endocrine mechanisms form further components of the acquired category. The authors connect abnormal self-renewal of cancer cells with metabolic changes needed to generate energy and note that metabolites can regulate signaling pathways and gene expression within tumors.

They cite a global analysis covering 1990 through 2019 that estimated 234 disability-adjusted life years per 100,000 person-years in 2019 for tumors attributable to metabolic risk factors, with high body mass index and high fasting glucose identified as major contributors. Endocrine tumors can arise in the pituitary, pancreas, thyroid, gastrointestinal tract or lungs and may secrete abnormal quantities of hormones or other signaling molecules, producing characteristic symptoms. The framework also recognizes that hormone effects are not confined to one cancer type because a tumor may express several hormone receptors simultaneously.

The psychological element is presented as an indirect influence rather than as a claim that anxiety or depression directly causes cancer. The article also discusses tumor–nerve interactions documented in breast cancer and argues that psychological factors deserve attention in comprehensive tumor care without treating them as isolated causes of malignancy. Combined-etiology tumors form the third category and are subdivided into innate–acquired and acquired–acquired combinations.

In an innate–acquired combination, inherited susceptibility interacts with one or more acquired risk factors. The commentary uses hereditary breast and ovarian cancer linked to BRCA1 and BRCA2 as an example, noting that mutations impairing DNA repair are associated with breast cancer risk three to seven times higher than in the general population. Radiation can add DNA damage, while smoking can increase risk through chemical carcinogens and epigenetic suppression.

Acquired–acquired combinations involve several acquired factors interacting over time. Examples in the article include an obese smoker with HPV-positive oropharyngeal cancer and an obese woman with high estrogen exposure who is at increased risk of endometrial cancer. The authors propose a three-part process for applying the framework.

A comprehensive history would examine family history and patterns of cancer across generations; smoking, alcohol use, diet and obesity; occupational and environmental exposures; infection status, including H. pylori , HPV and HBV; and psychological stress. Tumor and germline DNA sequencing would then identify high-penetrance pathogenic germline variants such as BRCA1/2, MLH1 and TP53. If no strong germline finding were present, the analysis would turn to somatic mutations or amplifications, viral DNA integration and mutational signatures linked with exposures such as smoking or aflatoxin.

The clinician would synthesize the molecular results with the history, classifying a case as innate when strong hereditary evidence is confirmed, acquired when there is a clear carcinogen or chronic-infection history without strong inherited predisposition, and combined etiology when genetic predisposition and acquired factors coexist or several acquired factors interact. The proposed synthesis is intended to make treatment planning more responsive to the reasons an individual tumor arose. A BRCA mutation carrier who smokes, the commentary suggests, would fit the combined-etiology category, linking genotype-directed treatment with smoking cessation.

In principle, this would allow management of the tumor to proceed alongside management of modifiable risks, supporting the framework’s stated aims of revealing etiology, improving diagnostic standards and informing more precise treatment plans. The authors nevertheless state that these therapeutic implications are preliminary and illustrative. They acknowledge that the classification incorporates established distinctions between hereditary and sporadic cancers, but argue that its distinctive feature is an integrative, action-oriented synthesis of genetic, environmental and metabolic information.

Dedicated investigations are still needed to establish evidence-based strategies for each tumor category and determine how the framework should be refined as additional clinical and molecular information becomes available.

Subject of Research: An integrative etiological framework for classifying tumors by inherited, acquired and combined causes

Article Title: New biological classification of tumors based on integrative medicine and its prospective clinical application

Article References: Zheng, S., Lu, Y., & Fan, D. (2026). New biological classification of tumors based on integrative medicine and its prospective clinical application. Holistic Integrative Oncology, 5(1), Article 84. https://doi.org/10.1007/s44178-026-00298-1

Image Credits: AI Generated

DOI: 10.1007/s44178-026-00298-1

Keywords: tumor classification, integrative medicine, innate tumors, acquired tumors, combined-etiology tumors, germline mutations, molecular profiling, environmental carcinogens, cancer prevention, holistic oncology, biological, classification