MASCC 2025 Highlights: Metabolomic Signatures May Predict CBD Response in Cancer Survivors with CIPN

At the MASCC 2025 Annual Meeting, Dr. Marialuisa Viganò from Canada introduced a compelling prospective observational study exploring how metabolomic signatures may help predict which cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN) are most likely to benefit from cannabidiol (CBD) treatment.

Chemotherapy-induced peripheral neuropathy (CIPN) remains a prevalent and disabling side effect of various anticancer agents, notably platinum-based drugs and taxanes. Current treatment options for CIPN are limited and often ineffective. Cannabidiol (CBD), a non-psychoactive component of cannabis, has been proposed as a potential therapeutic agent, with preliminary evidence suggesting symptom improvement in CIPN. However, its mechanism of action is poorly understood, and no validated biomarkers exist to predict therapeutic response.

Recently, metabolic pathway alterations have been implicated in CIPN pathogenesis (Hua et al., 2025), offering a new lens through which to evaluate treatment effects. This study aimed to assess whether untargeted metabolomic profiling of fecal samples could distinguish CBD responders from non-responders among cancer survivors with CIPN.

Background

Emerging research has highlighted disruptions in amino acid metabolism, oxidative stress pathways, and mitochondrial function in patients with CIPN, suggesting that metabolic dysregulation plays a central role in its pathophysiology. Hua et al. (2025) identified significant perturbations in several metabolic pathways—particularly those involving neurotransmitter precursors—in patients with CIPN compared to those without.

Given CBD’s reported impact on inflammation, oxidative stress modulation, mitochondrial activity, and neural signaling, understanding its downstream effects at the metabolic level could help stratify patients likely to benefit from treatment. This study by Vigano et al. (2024) adds to this growing field by integrating clinical outcomes with fecal metabolomic profiling to uncover predictive metabolic signatures.

Methods and Study Design

This prospective observational study enrolled 18 adult cancer survivors diagnosed with moderate-to-severe CIPN. Participants received oral cannabidiol up to 300 mg per day over two months. Stool samples were collected at baseline (pre-treatment) and after the 8-week treatment period.
The primary outcome was the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) score. A minimal clinically important difference (MCID) of 3.68 points was used to define CBD “responders” versus “non-responders.”

Metabolomic analysis was conducted using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) via the Q-Exactive Orbitrap platform. Data processing and pathway enrichment analysis were performed using MetaboAnalyst 6.0. Statistical significance was set at p<0.05.

Key Findings

Participants had a median age of 63 years, with a predominance of female (83%) breast (56%) and colorectal (17%) cancer survivors. More than 500 metabolites were significantly altered in response to CBD (linear model, p<0.05).

Hierarchical clustering demonstrated that CBD responders exhibited a higher relative abundance of several key metabolites compared to non-responders. Notably, five metabolic pathways were significantly modulated in responders:

• Tyrosine metabolism
• Phenylalanine, tyrosine, and tryptophan biosynthesis
• Lysine degradation
• Drug metabolism
• Ubiquinone and other terpenoid-quinone biosynthesis

Interestingly, two of these—phenylalanine/tyrosine/tryptophan biosynthesis and lysine degradation—have also been identified as differentially regulated in cancer patients with CIPN compared to those without (Hua et al., 2025), suggesting a possible shared pathophysiological mechanism.

Conclusion

This pilot study provides preliminary evidence that untargeted fecal metabolomics may identify metabolic signatures associated with a positive clinical response to cannabidiol in patients with CIPN, offering a non-invasive approach to treatment stratification. The observed overlap between altered pathways in CBD responders and previously reported CIPN-specific metabolic disturbances underscores the potential utility of these biomarkers in developing personalized supportive care strategies.

Such insights could pave the way for more targeted and effective symptom management. However, larger, rigorously designed trials with longer follow-up are essential to validate these findings, explore causality, and determine whether these metabolic profiles can be reliably used in routine clinical practice to guide CBD therapy in cancer survivors suffering from neuropathy.

MASCC 2025 Annual meeting