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Translational approaches to treatment-induced symptoms in cancer patients

Nature Reviews Clinical Oncology volume 9, pages 414–426 (2012)Cite this article

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Abstract

Cancer therapy makes patients sick. The therapies that are available to clinicians allow them to successfully control nausea, emesis and pain. However, this is not the case for a number of other symptoms that include fatigue, distractibility, poor memory, and diminished interest in previously pleasurable activities. These symptoms cluster during the course of cancer therapy and impair patient quality of life, limit therapy options and do not always resolve at the cessation of treatment. It is possible to describe the intensity and temporal features of symptoms and assess their relationship with the inflammatory response that is associated with cancer and cancer therapy. At the preclinical level, sophisticated animal models still need to be deployed to study the causal role of inflammation in specific components of cancer-related symptoms. Various approaches can be optimally combined in a translational symptom research pathway to provide a framework for assessing in a systematic manner the neurobehavioral toxicity of existing and newly developed cancer therapies. Ultimately, this knowledge will allow derivation of mechanism-based interventions to prevent or alleviate cancer-related symptoms.

Key Points

  • Overwhelming fatigue, distractibility, poor memory, and lack of interest in activities that used to be pleasurable are among the most distressing symptoms patients experience in response to cancer therapy

  • The trajectory of these symptoms can be studied over time together with their co-occurrence in the form of clusters and their impact on patients' daily functioning

  • There is already evidence that the development of cancer-related symptoms is associated with an increased expression of inflammatory mediators

  • Animal studies have confirmed that cancer therapy induces profound neurobehavioural changes that are associated with inflammation; attempts to model key symptoms in cancer patients are still scarce

  • Individual differences in symptom severity in response to cancer therapy provide a unique perspective on the genomics of symptoms that should be incorporated in animal models of cancer-related symptoms

  • Preclinical and clinical approaches can be combined in a translational research pathway that provides a framework for addressing the neurobehavioural toxicities of cancer therapies

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Figure 1: Symptom severity and symptom clusters in treated cancer patients.
Figure 2: Variation in symptom burden in patients treated for cancer.
Figure 3: Immune-to-brain communication pathways.
Figure 4: Role of proinflammatory cytokines.
Figure 5: Schematic of cancer-related symptoms modelled in animals.
Figure 6: Cancer-related fatigue and effort-related decision making.
Figure 7: Motivational assessment in mice.
Figure 8: Translational strategy of the pathophysiology of inflammation-associated depression.

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Acknowledgements

The research described was supported by Award Numbers R01 MH079829 and R01 NS073939 to R. Dantzer, and P01 CA124787 and R01 CA026582 to C. S. Cleeland, and R01-NS060822 to M. W. Meagher. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1450, Houston, 77030, TX, USA

    Robert Dantzer & Charles S. Cleeland

  2. Department of Psychology, College of Liberal Arts, Texas A&M University, 515 Coke Street, College Station, 77843-4235, TX, USA

    Mary W. Meagher

Authors
  1. Robert Dantzer
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  2. Mary W. Meagher
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  3. Charles S. Cleeland
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Contributions

All authors made a substantial contribution to researching data for the article, discussing content, and writing and editing the manuscript prior to submission, and revising the article after peer review.

Corresponding author

Correspondence to Robert Dantzer.

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Competing interests

R. Dantzer has received recent honoraria from Lundbeck Laboratories and Janssen. He is also a consultant for Lundbeck Laboratories. C. S. Cleeland has been a consultant/advisor for Abbott, Amgen, BMS-Bristol Myers Squibb, Exelixis, Genentech, and Pfizer. C. S. Cleeland has also received research funds from AstraZeneca. M. W. Meagher declares no competing interests.

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Dantzer, R., Meagher, M. & Cleeland, C. Translational approaches to treatment-induced symptoms in cancer patients. Nat Rev Clin Oncol 9, 414–426 (2012). https://doi.org/10.1038/nrclinonc.2012.88

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