Review: Cancer and schizophrenia: is there a paradox?

Hodgson, Richard; Wildgust, Hiram J; Bushe, Chris

doi:10.1177/1359786810385489

Cited by 76 publications

(73 citation statements)

References 100 publications

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“…This is confirmed by a disproportion in mortality from cardiac infarction or cancer in schizophrenia patients and in people without such diagnosis, unfavourable for the former, despite similar prevalence of these disorders (Kisely et al 2008, Hodgson et al 2010, Crump et al 2013). Furthermore, in people who died due to above causes, these disorders were significantly less often diagnosed in schizophrenia patients during their life, and this may indicate lower availability of screening tests and modern diagnostic methods.…”

Section: Discussionmentioning

confidence: 90%

Causes of Mortality in Schizophrenia: An Updated Review of European Studies

et al. 2017

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Section: Discussionmentioning

confidence: 90%

Causes of Mortality in Schizophrenia: An Updated Review of European Studies

et al. 2017

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“…The link between schizophrenia therapy and TLK inhibition is an interesting possibility because if the TLK-inhibiting properties of these drugs are effective against BCA, then one would expect that women who had been prescribed these drugs might display 1) a lower incidence of BCA compared to those who did not take the drugs and/or 2) an improved outcome after BCA diagnosis. While women with schizophrenia have multiple risk factors for BCA that might lead to expectations of a substantially increased risk (smoking, obesity, low exercise, poor diet, treatment-induced hyperprolactinemia), results of a systematic review of such studies 17 revealed that the incidence is decreased, similar, or only slightly increased from that of the general population. Various hypotheses have been proposed for such findings, including protective genetic effects [52][53][54][55] and antitumor properties of neuroleptics.…”

Section: Discussionmentioning

confidence: 99%

Phenothiazine Inhibitors of TLKs Affect Double-Strand Break Repair and DNA Damage Response Recovery and Potentiate Tumor Killing with Radiomimetic Therapy

et al. 2013

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The Tousled-like kinases (TLKs) are involved in chromatin assembly, DNA repair, and transcription. Two TLK genes exist in humans, and their expression is often dysregulated in cancer. TLKs phosphorylate Asf1 and Rad9, regulating double-strand break (DSB) repair and the DNA damage response (DDR). TLKs maintain genomic stability and are important therapeutic intervention targets. We identified specific inhibitors of TLKs from several compound libraries, some of which belong to the family of phenothiazine antipsychotics. The inhibitors prevented the TLK-mediated phosphorylation of Rad9(S328) and impaired checkpoint recovery and DSB repair. The inhibitor thioridazine (THD) potentiated tumor killing with chemotherapy and also had activity alone. Staining for γ-H2AX revealed few positive cells in untreated tumors, but large numbers in mice treated with low doxorubicin or THD alone, possibly the result of the accumulation of DSBs that are not promptly repaired as they may occur in the harsh tumor growth environment.

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“…Smoking is well known to increase the incidence of various types of cancer, including oral, stomach, liver, bladder, and lung cancer [2]; of these cancers, lung cancer has the highest mortality rate [3]. In addition, smoking and other cancer-related risk factors, such as alcohol abuse, obesity, and poor diet, are more common in schizophrenia patients than in the general population [4]. However, patients diagnosed with schizophrenia have a lower incidence of cancer than that observed in the general population [5,6,7,8].…”

Section: Introductionmentioning

confidence: 99%

Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

Yin

Lin²,

Chen³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. Methods: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. Results: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. Conclusions: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

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Review: Cancer and schizophrenia: is there a paradox?

Cited by 76 publications

References 100 publications

Causes of Mortality in Schizophrenia: An Updated Review of European Studies

Causes of Mortality in Schizophrenia: An Updated Review of European Studies

Phenothiazine Inhibitors of TLKs Affect Double-Strand Break Repair and DNA Damage Response Recovery and Potentiate Tumor Killing with Radiomimetic Therapy

Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

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