Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

doi:10.1007/s00520-025-09317-9

. 2025 Mar 6;33(4):254.

doi: 10.1007/s00520-025-09317-9.

Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

Raymond J Chan¹, Adam Walker², Janette Vardy³, Alexandre Chan⁴, Kate Oppegaard⁵, Yvette P Conley⁶, Steven M Paul⁷, Kord M Kober⁷, Carolyn Harris⁶, Joosun Shin⁸, Lisa Morse⁷, Ritu Roy⁹, Adam Olshen⁹, Marilyn J Hammer⁸, Jon D Levine⁹, Christine Miaskowski^{10

11

12}

Affiliations

¹ Flinders University, Bedford Park, Adelaide, South Australia, Australia.
² School of Clinical Medicine, University of New South Wales, Sydney, Australia.
³ Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁴ School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, CA, USA.
⁵ VA Portland Health Care System, Portland, OR, USA.
⁶ School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ School of Nursing, University of California, San Francisco, CA, USA.
⁸ Dana Farber Cancer Institute, Boston, MA, USA.
⁹ School of Medicine, University of California, San Francisco, CA, USA.
¹⁰ School of Nursing, University of California, San Francisco, CA, USA. [email protected].
¹¹ School of Medicine, University of California, San Francisco, CA, USA. [email protected].
¹² Department of Physiological Nursing, University of California, San Francisco, 490 Illinois Street, Floor 12, San Francisco, CA, 94143, USA. [email protected].

PMID: 40047999
PMCID: PMC11885406
DOI: 10.1007/s00520-025-09317-9

Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

Raymond J Chan et al. Support Care Cancer. 2025.

. 2025 Mar 6;33(4):254.

doi: 10.1007/s00520-025-09317-9.

Authors

Affiliations

¹ Flinders University, Bedford Park, Adelaide, South Australia, Australia.
² School of Clinical Medicine, University of New South Wales, Sydney, Australia.
³ Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
⁴ School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, CA, USA.
⁵ VA Portland Health Care System, Portland, OR, USA.
⁶ School of Nursing, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ School of Nursing, University of California, San Francisco, CA, USA.
⁸ Dana Farber Cancer Institute, Boston, MA, USA.
⁹ School of Medicine, University of California, San Francisco, CA, USA.
¹⁰ School of Nursing, University of California, San Francisco, CA, USA. [email protected].
¹¹ School of Medicine, University of California, San Francisco, CA, USA. [email protected].
¹² Department of Physiological Nursing, University of California, San Francisco, 490 Illinois Street, Floor 12, San Francisco, CA, 94143, USA. [email protected].

PMID: 40047999
PMCID: PMC11885406
DOI: 10.1007/s00520-025-09317-9

Abstract

Purpose: This study reports on the results from our data-driven approach that identified perturbations in neuroactive ligand-receptor interaction and renin-angiotensin system (RAS) pathways in oncology patients with and without self-reported cancer-related cognitive impairment (CRCI).

Methods: In a sample of oncology patients receiving chemotherapy (n = 1343), the Attentional Function Index (AFI) was used to assess CRCI. Patients were grouped into low (AFI score of < 5) versus high (AFI score of > 7.5) levels of cognitive function. Gene expression analyses were done using RNA-seq (n = 185) and microarray (n = 158) technologies. Pathway impact analysis was used to evaluate for perturbations in biological pathways associated with self-reported CRCI.

Results: The combined pathway impact analysis revealed that the neuroactive ligand-receptor interaction and RAS pathways were significantly perturbed between the patients with low versus high AFI scores.

Conclusions: Findings from this study suggest that in addition to inflammatory pathways, numerous mechanisms may contribute to the underlying mechanisms for the development and/or persistence of self-reported CRCI.

Keywords: Cancer; Chemotherapy; Cognitive dysfunction; Cognitive impairment; Neuroinflammation; Renin angiotensin system.

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Conflict of interest statement

Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Committee on Human Research at the University of California, San Francisco. Consent to participate: Written informed consent was obtained from the patients. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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References

1. Cerulla Torrente N, Navarro Pastor JB, de la Osa CN (2020) Systematic review of cognitive sequelae of non-central nervous system cancer and cancer therapy. J Cancer Surviv 14(4):464–482. 10.1007/s11764-020-00870-2 - PubMed
1. Klaver KM, Duijts SFA, Engelhardt EG, Geusgens CAV, Aarts MJB, Ponds R et al (2020) Cancer-related cognitive problems at work: experiences of survivors and professionals. J Cancer Surviv 14(2):168–178. 10.1007/s11764-019-00830-5 - PMC - PubMed
1. Tan CJ, Yip SYC, Chan RJ, Chew L, Chan A (2021) Investigating how cancer-related symptoms influence work outcomes among cancer survivors: a systematic review. J Cancer Surviv. 10.1007/s11764-021-01097-5 - PMC - PubMed
1. Cheung YT, Shwe M, Tan YP, Fan G, Ng R, Chan A (2012) Cognitive changes in multiethnic Asian breast cancer patients: a focus group study. Ann Oncol 23(10):2547–2552. 10.1093/annonc/mds029 - PubMed
1. Ren X, Boriero D, Chaiswing L, Bondada S, St. Clair DK, Butterfield DA (2019) Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”), a condition that significantly impairs the quality of life of many cancer survivors. Biochimica et Biophysica Acta (BBA) – Mol Basis Dis 1865(6):1088–97. 10.1016/j.bbadis.2019.02.007 - PMC - PubMed

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[1] Cerulla Torrente N, Navarro Pastor JB, de la Osa CN (2020) Systematic review of cognitive sequelae of non-central nervous system cancer and cancer therapy. J Cancer Surviv 14(4):464–482. 10.1007/s11764-020-00870-2 - PubMed

[2] Cerulla Torrente N, Navarro Pastor JB, de la Osa CN (2020) Systematic review of cognitive sequelae of non-central nervous system cancer and cancer therapy. J Cancer Surviv 14(4):464–482. 10.1007/s11764-020-00870-2 - PubMed

[3] Klaver KM, Duijts SFA, Engelhardt EG, Geusgens CAV, Aarts MJB, Ponds R et al (2020) Cancer-related cognitive problems at work: experiences of survivors and professionals. J Cancer Surviv 14(2):168–178. 10.1007/s11764-019-00830-5 - PMC - PubMed

[4] Klaver KM, Duijts SFA, Engelhardt EG, Geusgens CAV, Aarts MJB, Ponds R et al (2020) Cancer-related cognitive problems at work: experiences of survivors and professionals. J Cancer Surviv 14(2):168–178. 10.1007/s11764-019-00830-5 - PMC - PubMed

[5] Tan CJ, Yip SYC, Chan RJ, Chew L, Chan A (2021) Investigating how cancer-related symptoms influence work outcomes among cancer survivors: a systematic review. J Cancer Surviv. 10.1007/s11764-021-01097-5 - PMC - PubMed

[6] Tan CJ, Yip SYC, Chan RJ, Chew L, Chan A (2021) Investigating how cancer-related symptoms influence work outcomes among cancer survivors: a systematic review. J Cancer Surviv. 10.1007/s11764-021-01097-5 - PMC - PubMed

[7] Cheung YT, Shwe M, Tan YP, Fan G, Ng R, Chan A (2012) Cognitive changes in multiethnic Asian breast cancer patients: a focus group study. Ann Oncol 23(10):2547–2552. 10.1093/annonc/mds029 - PubMed

[8] Cheung YT, Shwe M, Tan YP, Fan G, Ng R, Chan A (2012) Cognitive changes in multiethnic Asian breast cancer patients: a focus group study. Ann Oncol 23(10):2547–2552. 10.1093/annonc/mds029 - PubMed

[9] Ren X, Boriero D, Chaiswing L, Bondada S, St. Clair DK, Butterfield DA (2019) Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”), a condition that significantly impairs the quality of life of many cancer survivors. Biochimica et Biophysica Acta (BBA) – Mol Basis Dis 1865(6):1088–97. 10.1016/j.bbadis.2019.02.007 - PMC - PubMed

[10] Ren X, Boriero D, Chaiswing L, Bondada S, St. Clair DK, Butterfield DA (2019) Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”), a condition that significantly impairs the quality of life of many cancer survivors. Biochimica et Biophysica Acta (BBA) – Mol Basis Dis 1865(6):1088–97. 10.1016/j.bbadis.2019.02.007 - PMC - PubMed

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Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

Affiliations

Perturbations in the neuroactive ligand-receptor interaction and renin angiotensin system pathways are associated with cancer-related cognitive impairment

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