Porporato · Oncogenesis 2016 · narrative review · n=?

Understanding cachexia as a cancer metabolism syndrome.

Cited 560 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of biological mechanisms without systematic review methodology or new human clinical data.

PubMed 26900952 · doi:10.1038/oncsis.2016.3 · record verified 2026-08-27

What was done

This narrative review describes the metabolic basis of cancer cachexia, focusing on how systemic metabolic reprogramming, host tissue wasting (skeletal muscle and adipose tissue), and tumor-secreted factors fuel tumor proliferation and impair multi-organ function.

What was found

The authors note that cancer cachexia is estimated to be the direct cause of at least 20% of cancer deaths. The condition is characterized by relentless muscle and fat wasting despite adequate caloric intake, nutrient mobilization (direct lipid and amino acid release, plus indirect glucose production via hepatic gluconeogenesis), insulin/IGF-1 resistance, mitochondrial uncoupling, and white adipose tissue browning leading to elevated resting energy expenditure. In cancers such as pancreatic cancer, wasting markers can precede clinical tumor detection, driven in part by tumor-secreted mediators such as parathyroid hormone-related protein (PTHrP) and microRNAs. No additional quantitative trial data are reported in the abstract.

Why it matters

It emphasizes that cachexia is an active driver of tumor growth and mortality rather than merely an end-stage epiphenomenon, highlighting metabolic targets for potential therapeutic intervention.

Limits

This is an unsystematic narrative overview based largely on preclinical and mechanistic models rather than a systematic synthesis of human clinical trial evidence. No primary clinical datasets, statistical effect sizes, or trial-specific outcome measures are reported in the abstract.

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