The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer: who can benefit from ketoconazole therapy?

Lin, Guorong; Yao, Xu; Ye, Ding Wei; Zhu, Yao; Zhang, Shi Lin; Dai, Bo; Zhang, Hai Liang; Shen, Yi; Guang, Chun

doi:10.1038/aja.2012.57

Cited by 13 publications

(6 citation statements)

References 25 publications

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“…A full-text review was performed for 178 potentially relevant articles. After evaluating the selection criteria, we identified 11 articles with 4206 patients for systematic review and ten articles with 4136 patients for meta-analysis [8][9][10][23][24][25][26][27][28][29][30]. Figure 1 depicts the selection process and list.…”

Section: Literature Searchmentioning

confidence: 99%

Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis

et al. 2020

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Introduction This systematic review and meta-analysis aimed to assess the prognostic value of testosterone in patients with castration-resistant prostate cancer (CRPC). Materials and methods PubMed, Web of Science, and Scopus databases were systematically searched until December 2019, according to the Preferred Reporting Items for Systemic Review and Meta-analysis statement. The endpoints were progression-free survival (PFS) and overall survival (OS). Results We identified 11 articles with 4206 patients for systematic review and nine articles with 4136 patients for meta-analysis. Higher testosterone levels were significantly associated with better OS (pooled HR 0.74, 95% CI 0.58–0.95) and better PFS (pooled HR 0.51, 95% CI 0.30–0.87). Subgroup analyses based on the treatment type revealed that higher testosterone levels were significantly associated with better OS in CRPC patients treated with androgen receptor-targeted agents (ARTAs) (pooled HR 0.64, 95% CI 0.55–0.75), but not in those treated with chemotherapy (pooled HR 0.78, 95% CI 0.53–1.14). Conclusion This meta-analysis demonstrated that the PFS and OS were significantly greater in patients with CRPC in those with higher testosterone levels than that of those with lower testosterone levels. In the subgroup analyses, lower testosterone levels were a consistently poor prognostic factor for OS in patients treated with ARTAs, but not in those treated with chemotherapy. Therefore, higher testosterone levels could be a useful biomarker to identify patient subgroups in which ARTAs should be preferentially recommended in the CRPC setting.

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Section: Literature Searchmentioning

confidence: 99%

Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis

et al. 2020

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“…Ketoconazole inhibits adrenal testosterone synthesis through the inhibition of cytochrome P450 14α‐demethylase 44 . This implies that Ketoconazole could function in the treatment of metastatic, castration‐resistant prostate cancer, leading to improved survival 45 . In renal cancer, which has increased expression of NFX1‐123 (Figure 1), Ketoconazole has been shown to be an inhibitor of exosome production, and as an adjunct therapy, Ketoconazole potentiates the effectiveness of Sunitinib by decreasing tumor cell proliferation, and the clonogenic potential of renal cancer cell lines 46 …”

Section: Discussionmentioning

confidence: 99%

NFX1‐123: A potential therapeutic target in cervical cancer

Chintala,

Dankoski,

Anbarasu

et al. 2023

Journal of Medical Virology

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NFX1‐123 is a splice variant isoform of the NFX1 gene. It is highly expressed in cervical cancers caused by HPV, and NFX1‐123 is a protein partner with the HPV oncoprotein E6. Together, NFX1‐123 and E6 affect cellular growth, longevity, and differentiation. The expression status of NFX1‐123 in cancers beyond cervical and head and neck cancers, and its potential as therapeutic target, have not been investigated. TSVdb of TCGA was used to quantify NFX1‐123 expression in 24 cancers compared with normal tissues. The NFX1‐123 protein structure was predicted and then submitted to retrieve suitable drug molecules. The top four compounds, found to bind in silico to NFX1‐123, were tested experimentally to determine their effects on NFX1‐123‐related cellular growth, survival, and migration. 46% of cancers (11 of 24 had significant differences in NFX1‐123 expression, with nine having had greater NFX1‐123 expression, when compared with adjacent normal tissues. Bioinformatics and proteomic predictive analysis modeled the three‐dimensional structure of NFX1‐123, and drug libraries were screened for high‐binding affinity compounds using this modeled structure. Seventeen drugs with binding energies ranging from −1.3 to −10 Kcal/mol were identified. The top four compounds were used to treat HPV‐ and HPV+ cervical cancer cell lines, three of which (Ropitoin, R428 and Ketoconazole) reduced NFX1‐123 protein levels, inhibited cellular growth, survival, and migration, and enhanced the cytotoxicity of Cisplatin. These findings highlight cancers expressing high levels of NFX1‐123, and drugs that target it, may reduce cellular growth, survival, and migration, making NFX1‐123 a potential novel therapeutic target.

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“… 8 The PSADT was calculated as the PSA kinetics over time from the nadir PSA to the baseline PSA, on the basis of the previous literature. 9 …”

Section: Methodsmentioning

confidence: 99%

Development of a preliminary nomogram to predict progression of bone scan for castration-resistant prostate cancer

Lin¹,

Ye²,

Jia³

et al. 2015

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The optimal time to perform bone scan to detect new metastasis during the castration-resistant prostate cancer (CRPC) stage remains undefined. This study attempted to identify predictors of progression of bone scan for CRPC, and use such information to develop a nomogram to predict the optimal time of examinations for bone scan. The analysis included 167 CRPC patients. Progression of bone lesion, as evaluated by bone scan, occurred in 64 (38.3%) cases. A logistic regression identified the following three risk factors: short time to prostate-specific antigen (PSA) progression, severe pain, and short PSA doubling time (PSADT) (P<0.05 for all). A nomogram model was constructed to predict progression of bone scan using time to PSA progression and severe pain as dichotomized variables and PSADT as a continuous variable. The result indicated that a predictive nomogram model showed a bootstrap-corrected concordance index of 0.762 and good calibration using the three readily available variables, and there were worse prognosis and higher progression rate of bone scan for patients with time to PSA progression <6.6 months, severe pain, and short PSADT (<2 months). In conclusion, short time to PSA progression, severe pain, and short PSADT are three risk factors of progression of bone scan for CRPC patients. The predictive nomogram model may be a valuable numerical assessment tool for patient consultation and treatment decision.

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The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer: who can benefit from ketoconazole therapy?

Cited by 13 publications

References 25 publications

Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis

Prognostic value of testosterone for the castration-resistant prostate cancer patients: a systematic review and meta-analysis

NFX1‐123: A potential therapeutic target in cervical cancer

Development of a preliminary nomogram to predict progression of bone scan for castration-resistant prostate cancer

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