TY - CHAP
T1 - Chemobrain
T2 - An accelerated aging process linking adenosine A2A receptor signaling in cancer survivors
AU - Oliveros, Alfredo
AU - Poleschuk, Michael
AU - Cole, Peter D.
AU - Boison, Detlev
AU - Jang, Mi Hyeon
N1 - Publisher Copyright:
© 2023
PY - 2023/1
Y1 - 2023/1
N2 - Chemotherapy has a significant positive impact in cancer treatment outcomes, reducing recurrence and mortality. However, many cancer surviving children and adults suffer from aberrant chemotherapy neurotoxic effects on learning, memory, attention, executive functioning, and processing speed. This chemotherapy-induced cognitive impairment (CICI) is referred to as “chemobrain” or “chemofog”. While the underlying mechanisms mediating CICI are still unclear, there is strong evidence that chemotherapy accelerates the biological aging process, manifesting as effects which include telomere shortening, epigenetic dysregulation, oxidative stress, mitochondrial defects, impaired neurogenesis, and neuroinflammation, all of which are known to contribute to increased anxiety and neurocognitive decline. Despite the increased prevalence of CICI, there exists a lack of mechanistic understanding by which chemotherapy detrimentally affects cognition in cancer survivors. Moreover, there are no approved therapeutic interventions for this condition. To address this gap in knowledge, this review attempts to identify how adenosine signaling, particularly through the adenosine A2A receptor, can be an essential tool to attenuate accelerated aging phenotypes. Importantly, the adenosine A2A receptor uniquely stands at the crossroads of cancer treatment and improved cognition, given that it is widely known to control tumor induced immunosuppression in the tumor microenvironment, while also posited to be an essential regulator of cognition in neurodegenerative disease. Consequently, we propose that the adenosine A2A receptor may provide a multifaceted therapeutic strategy to enhance anticancer activity, while combating chemotherapy induced cognitive deficits, both which are essential to provide novel therapeutic interventions against accelerated aging in cancer survivors.
AB - Chemotherapy has a significant positive impact in cancer treatment outcomes, reducing recurrence and mortality. However, many cancer surviving children and adults suffer from aberrant chemotherapy neurotoxic effects on learning, memory, attention, executive functioning, and processing speed. This chemotherapy-induced cognitive impairment (CICI) is referred to as “chemobrain” or “chemofog”. While the underlying mechanisms mediating CICI are still unclear, there is strong evidence that chemotherapy accelerates the biological aging process, manifesting as effects which include telomere shortening, epigenetic dysregulation, oxidative stress, mitochondrial defects, impaired neurogenesis, and neuroinflammation, all of which are known to contribute to increased anxiety and neurocognitive decline. Despite the increased prevalence of CICI, there exists a lack of mechanistic understanding by which chemotherapy detrimentally affects cognition in cancer survivors. Moreover, there are no approved therapeutic interventions for this condition. To address this gap in knowledge, this review attempts to identify how adenosine signaling, particularly through the adenosine A2A receptor, can be an essential tool to attenuate accelerated aging phenotypes. Importantly, the adenosine A2A receptor uniquely stands at the crossroads of cancer treatment and improved cognition, given that it is widely known to control tumor induced immunosuppression in the tumor microenvironment, while also posited to be an essential regulator of cognition in neurodegenerative disease. Consequently, we propose that the adenosine A2A receptor may provide a multifaceted therapeutic strategy to enhance anticancer activity, while combating chemotherapy induced cognitive deficits, both which are essential to provide novel therapeutic interventions against accelerated aging in cancer survivors.
KW - Adenosine A receptor
KW - Aging
KW - Cancer
KW - Cancer survivors
KW - Chemobrain
KW - Chemotherapy-induced cognitive impairment
UR - http://www.scopus.com/inward/record.url?scp=85169037902&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85169037902&partnerID=8YFLogxK
U2 - 10.1016/bs.irn.2023.08.003
DO - 10.1016/bs.irn.2023.08.003
M3 - Chapter
C2 - 37741694
AN - SCOPUS:85169037902
SN - 9780443186677
T3 - International Review of Neurobiology
SP - 267
EP - 305
BT - Adenosine A Receptor Antagonists
A2 - Chen, Jiang-Fan
A2 - Mori, Akihisa
PB - Academic Press Inc
ER -