Biomarkers associated with “chemobrain”

NUS clinician scientists have identified biomarkers associated with cancer-related cognitive impairment to provide better supportive care for cancer patients and survivors.

Cancer-related cognitive impairment, also known as chemobrain, is a complication arising from cancer and cancer treatment that adversely affects the daily lives of cancer patients and survivors. This medical condition can occur in one out of three breast cancer patients who have completed their chemotherapy treatment. Many cancer survivors have reported cognitive difficulties relating to memory and attention, which affect their ability to carry out daily functions and their capacity to work. However, for early medical interventions, there are limited strategies available to identify patients at a greater risk of developing such symptoms.

Prof Alexandre CHAN from the Department of Pharmacy, NUS and his research team have found that breast cancer patients carrying the Val66Met gene variation have a lower risk of developing impairment in their cognitive functions, particularly in the areas of memory, multitasking and verbal ability. This gene variation is a genetic polymorphism of the brain-derived neurotrophic factor (BDNF). The team had previously reported that it could be associated with a lower risk for chemobrain among breast cancer patients receiving chemotherapy. The current study builds on their previous work and involved more than 190 patients over a period of four years at three cancer centres in Singapore.

In another related study, the researchers found that breast cancer patients with higher levels of dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS) in their body prior to chemotherapy treatment have a lower risk of developing cognitive impairment in the areas of verbal fluency and mental acuity. DHEA is a steroid hormone that is produced naturally in the human body. Both DHEA and DHEAS are known to have important functions to help regulate brain function and behaviour.

These findings contribute to the understanding of the underlying biological pathways related to chemobrain. By identifying the clinically relevant factors which predispose cancer patients to the onset of chemobrain, better interventions can be tailored accordingly to those who are at a higher risk of developing cognitive impairment.

Prof Chan said, “Currently available pharmacological and non-pharmacological interventions to address and manage chemobrain have limited effectiveness. Being able to monitor chemobrain and its related symptoms through suitable biomarkers represents the first step to addressing this issue.”

He added, “Our team is exploring potential therapeutic interventions that may provide viable options to mitigate post-treatment complications (not limited to chemobrain) that cancer survivors are experiencing, with the overall goal to improve their quality of life.”

Figure shows the biomarkers associated with chemobrain that are currently under investigation by Prof Alex Chan’s research group.

References

CJ Tan; SWT Lim; YL Toh; T Ng; A Yeo; M Shwe; KM Foo; P Chu; A Jain; SL Koo; RA Dent; RCH Ng; YS Yap; EH Lim; KWJ Loh; WYChay; GE Lee; TJY Tan; SY Beh; M Wong; JJ Chan; CC Khor; HK Ho; A Chan*, “Replication and Meta-analysis of the Association between BDNF Val66Met Polymorphism and Cognitive Impairment in Patients Receiving Chemotherapy” MOLECULAR NEUROBIOLOGY DOI: 10.1007/s12035-018-1410-4 Published: 2018.

YL Toh; JS Mujtaba; S Bansal; A Yeo; M Shwe; AJ Lau; A Chan*, “Prechemotherapy Levels of Plasma Dehydroepiandrosterone and Its Sulfated Form as Predictors of Cancer‐Related Cognitive Impairment in Patients with Breast Cancer Receiving Chemotherapy” PHARMACOTHERAPY DOI: 10.1002/phar.2259 Published: 2019.