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PI: Wang (Contact), Penedo, Cella
Summary:
This pilot project will collect preliminary data toward the goal of developing a program aimed at studying precise mechanisms of cancer and cancer-treatment related cognitive impairments (CRCI) and developing treatment strategies targeting the mechanisms. We will study prostate cancer and breast cancer survivors by collecting and analyzing neuroimaging, cognitive, psychosocial stress, and inflammation data before and after initiation of adjuvant therapy.
Funding:
Details:
A significant number of cancer survivors with non-central nervous system (non-CNS) tumors have reported cognitive problems related to adjuvant or neoadjuvant treatment. The complaints range from memory, attention, multitasking, and planning, to problems following directions. These problems can start shortly after receiving treatment and in some cases last for years. These cancer and cancer-treatment related cognitive impairments (CRCI) have been reported by many women and men treated for breast and prostate cancer, respectively. In addition to the neurotoxic effects of cancer treatment, CRCI may also be exacerbated by ongoing psychosocial stressors via their effect on neuroimmune regulation and inflammation.
Neuroimaging studies have provided unequivocal evidence that cancer and cancer treatments, particularly systemic cytotoxic chemotherapy, are associated with changes in the brain networks that are responsible for the cognitive functions reported to be declining in cancer survivors. However, the mechanisms underlying these changes have not been well studied and as a consequence, are poorly understood. This information is essential for developing markers to inform intervention and care strategies. It is likely that the mechanisms include several interacting pathways, and its complexity is further enhanced by individual variability. One such likely mechanistic pathway is through the increased inflammatory responses due to cancer and treatment-related stress, and in turn their effects on the brain. Our working hypothesis is that psychosocial stressors related to cancer and cancer-treatments induce increased inflammation that impact brain networks important to cognition.
In this project, we will collect preliminary evidence to show that inflammation is related to brain network damage or compensation, or both, in cancer patients receiving adjuvant therapy, and demonstrate common pathways across prostate and breast cancer survivors receiving hormonal or chemotherapy treatments, and characterize how different cancers and treatments may impact CRCI and via different mechanisms. Outcome of this research will be used to establish a larger program project (i.e., ASURE) aimed at 1) understanding the mechanisms linking cancer and treatment-related stressors, inflammation, brain network integrity, and function of cancer patients, 2) characterizing commonalities and distinctions of these relationships across different types of cancer and cancer treatments, and 3) developing treatment strategies targeting these mechanisms using cognitive-based psychological intervention and/or repetitive transcranial magnetic stimulation (rTMS).