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Tumor Discovery The mechanism of cancer-related cognitive decline

which, in turn, led to mitochondrial swelling and rupture Immunotherapies mainly comprising immune checkpoint
and induced oxidative stress in the brain tissue . inhibitors and chimeric antigen receptor T-cell (CAR-T)
[62]
Methotrexate increases the level of malondialdehyde in therapy are the most promising approaches for cancer
rat cerebellum by interacting with enzymes in the folate treatment to date. At present, the evidence of cognitive
[63]
metabolic pathway, thereby inducing oxidative stress . impairment caused by antitumor drugs is mostly focused
Chemotherapy-activated oxidative stress (accumulation on chemotherapy and targeted therapy, and there is still a
of reactive oxygen species) induces mitochondrial DNA lack of basic and clinical studies on the relationship between
mutations and reduces the antioxidant capacity of CNS, immunotherapy and cognitive function [72,73] . This may be
resulting in cognitive impairment . In addition, it damages attributed to the frequent use of novel antitumor therapies
[64]
the cerebral vasculature by exacerbating thrombosis in combination with other therapies, small sample sizes for
and interfering with cerebral small vessel perfusion or clinical studies, and difficulty in excluding the interference
activating transcription factor 3-mediated lipotoxic brain of chemotherapy or radiotherapy with cognitive function .
[74]
microvascular injury, resulting in cognitive impairment by A prospective multicenter phase II clinical trial showed that
a mechanism similar to that of vascular dementia . patients with refractory large B-cell lymphoma treated with
[65]
CAR-T therapy might develop neurological symptoms, such
3.2. Other adjuvant therapies as delirium, cognitive impairment and encephalopathy,
[75]
In addition to chemotherapy, hormonal therapy, or myelosuppression, and cytokine release syndrome (CRS) .
endocrine therapy, targeted therapies such as those with CAR-T therapy leads to CRS by activating T lymphocytes
anti-angiogenic agents, and immunotherapy can also and recruiting neighboring immune cells to release a range
cause cognitive impairment. Endocrine therapies for breast of inflammatory factors and CSFs, thus affecting multiple
cancer include selective estrogen receptor modulators organs and systems including the CNS [76,77] . Radiotherapy
(e.g., tamoxifen) and aromatase inhibitors (e.g., letrozole). is a crucial treatment modality for metastatic tumors as
Tamoxifen treatment can affect specific cognitive domains well as head and neck malignancies. It has been established
such as memory, language function, executive functions, that radiotherapy parameters have a negative impact on the
and processing speed in patients with breast cancer . cognitive function, including total dose, dose per fraction,
[66]
[78]
Cell line models showed that tamoxifen could not only and treated volume . A cohort study by McDowell
[79]
affect the neuronal activity by modulating exocytosis and et al. showed that a moderate to high proportion of
catecholamine storage in vesicles but also acts on voltage- patients with nasopharyngeal carcinoma treated with
gated potassium channels to interfere with the secretion of intensive radiotherapy developed cognitive impairment
neurotransmitters, thereby affecting cognitive function . and psychobehavioral abnormalities, particularly apathy,
[67]
Spatial working memory impairment was observed in disinhibition, and executive dysfunction. A cross-sectional
primates after letrozole administration, which might be study of 78 patients with primary brain tumors treated
related to increased estradiol levels and reduced neuronal with radiotherapy showed that hippocampal tissues were
excitability in the hippocampus after drug administration . susceptible to radiotherapy, and high-dose radiation to
[68]
A prospective study showed that approximately 31.03% the left hippocampus led to impaired verbal learning and
[80]
(18/58) of 75 patients with metastatic renal cell carcinoma memory . A systematic review suggested that acute
receiving targeted therapy suffered from the impairments radiotherapy could synergistically alter the signaling
in information processing and working memory unrelated microenvironment in progenitor cell niches in the brain and
[69]
[70]
to fatigue . A cross-sectional study by Mulder et al. hippocampus by triggering CNS inflammation, damaging
compared the cognitive functions of patients with metastatic neuronal lineages and glial cells and their progenitors,
renal cell carcinoma or gastrointestinal stromal tumors and disrupting the integrity of the supporting structures,
receiving targeted therapy with vascular endothelial growth thereby causing progressive neuronal loss and cognitive
[81]
factor receptor (VEGFR) inhibitors (sunitinib or sorafenib), impairment .
patients with untreated metastatic renal cell carcinoma, and 4. Common risk factors for cancer and
healthy controls. They found that the cognitive functions, cognitive impairment
particularly learning, memory, and executive functions,
were significantly reduced in cancer patients. Moreover, Aging is a common risk factor for many diseases, including
these cognitive impairments were more severe in the cancer cancer and neurodegenerative disorders. It is believed that
patients receiving anti-angiogenic therapy than in those cumulative adverse reactions lead to genomic instability,
receiving others. Targeted anti-angiogenic agents, such as mitochondrial dysfunction, DNA damage, or impaired
sunitinib, may induce cognitive impairment by blocking DNA repair process . Cancer and neurodegeneration
[82]
VEGFR2 signaling, autophagy, and overactive apoptosis . with cognitive impairment may share common signal
[71]
Volume 1 Issue 1 (2022) 5 https://doi.org/10.36922/td.v1i1.46