Repurposing Antipsychotics of the Diphenylbutylpiperidine Class for Cancer Therapy

Publication date: Available online 13 October 2019Source: Seminars in Cancer BiologyAuthor(s): Vikram Shaw, Suyash Srivastava, Sanjay K. SrivastavaAbstractThe recent development of high throughput compound screening has allowed drug repurposing to emerge as an effective avenue for discovering novel treatments for cancer. FDA-approved antipsychotic drugs fluspirilene, penfluridol, and pimozide are clinically used for the treatment of psychotic disorders, primarily schizophrenia. These compounds, belong to diphenylbutylpiperidine class of antipsychotic drugs, are the potent inhibitors of dopamine D2 receptor and calcium channel. A correlation has been found that patients treated for schizophrenia have lower incidences of certain types of cancer, such as respiratory, prostate, and bladder cancers. These compounds have also been shown to inhibit cancer proliferation in a variety of cancer cells, including melanoma, lung carcinoma, breast cancer, pancreatic cancer, glioma, and prostate cancer, among others. Antipsychotic drugs induce apoptosis and suppress metastasis in in vitro and in vivo models through mechanisms involving p53, STAT3, STAT5, protein phosphatase 2A, cholesterol homeostasis, integrins, autophagy, USP1, wnt/β-catenin signaling, and DNA repair. Additionally, pre-clinical evidence suggests that penfluridol and pimozide act synergistically with existing chemotherapeutic agents, such as dasatinib, temozolomide, and cisplatin. Some studies have also reported that ...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research

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CONCLUSION: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology. PMID: 32935638 [PubMed - as supplied by publisher]
Source: Tumori - Category: Cancer & Oncology Tags: Tumori Source Type: research
Authors: Zhang XY, Zhang PY Abstract [This retracts the article DOI: 10.3892/ol.2016.5107.]. PMID: 32934752 [PubMed - in process]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Zhang XY, Zhang PY Abstract [This retracts the article DOI: 10.3892/ol.2016.5093.]. PMID: 32934751 [PubMed - in process]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Wan S, Zhao H Abstract The present study aimed to explore the diagnostic and prognostic value of lncRNA maternally expressed 3 (MEG3) in cervical cancer. Eighty-four patients with cervical cancer from February 2013 to March 2014 were enrolled in the observation group (OG), and another 58 female subjects who underwent physical examination at Huangshi Central Hospital were enrolled as the control group (CG). The serum MEG3 expression of patients in the two groups was detected by RT-qPCR, and the ability of MEG3 to aid in the diagnosis of cervical cancer, lymph node metastasis and FIGO staging, as well as to ...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, SLC17A9 can be used as a new molecular marker to predict the poor prognosis of patients with HCC. PMID: 32934749 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, the present study revealed that linalool inhibits T-ALL cell survival with involvement of the MAPK signaling pathway. JNK activation and ERK inhibition may play a functional role in apoptosis induction of T-ALL cells. Linalool may be developed as a novel anti T-ALL agent. PMID: 32934748 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, psychological stress was more prominent in younger patients with stage IV breast cancer treated with hormonal therapy compared with elderly patients. Importantly, improving QOL within the 3 months after treatment initiation could lead to longer PFS rate. PMID: 32934747 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Authors: Verma A, Najahi-Missaoui W, Cummings BS, Somanath PR Abstract Metastatic prostate cancer (PCa) has a very high mortality rate in men, in Western countries and lacks reliable treatment. The advanced-stage PCa cells overexpress P21 (RAC1) activated kinase-1 (PAK1) and secreted phospholipase A2 (sPLA2) suggesting the potential utility of pharmacologically targeting these molecules to treat metastatic PCa. The small molecule, inhibitor targeting PAK1 activation-3 (IPA3) is a highly specific allosteric inhibitor of PAK1; however, it is metabolically unstable once in the plasma thus, limiting its utility as a ch...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Antitumor effects of ribavirin in combination with TMZ and IFN-β in malignant glioma cells. Oncol Lett. 2020 Nov;20(5):178 Authors: Ochiai Y, Sumi K, Sano E, Yoshimura S, Yamamuro S, Ogino A, Ueda T, Suzuki Y, Nakayama T, Hara H, Katayama Y, Yoshino A Abstract The prognosis of gioblastoma, the standard chemotherapy agent for which is temozolomide (TMZ), remains poor despite recent advances in multimodal treatments. Therefore, it is necessary to identify and develop novel therapeutics for this malignant disease. Ribavirin, an anti-viral agent which is one of the standard agents for treatment of chr...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
In conclusion, high expression levels of eIF4A2 are associated with a poor prognosis and may be used as a potential prognostic indicator in patients with ESCC. PMID: 32934744 [PubMed]
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
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