Patient-reported outcomes in metastatic castration-resistant prostate cancer

Fallowfield, Lesley; Payne, Heather; Jenkins, Valerie

doi:10.1038/nrclinonc.2016.100

Cited by 30 publications

(23 citation statements)

References 46 publications

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“…Prostate cancer (PCa) is the second leading cause of cancer-related death among males in both developed and less developed countries, including China (1,2). Patients with PCa predominantly die from metastatic disease when the cancer becomes resistant to androgen deprivation therapy, which is termed castration-resistant PCa (CRPC) (3). Epithelial-to-mesenchymal transition (EMT) is a prerequisite for cancer invasion into the surrounding tissue (4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

Yang

Zhang

et al. 2020

Front. Oncol.

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The transcription factor E2F1 regulates the expression of the miR-20b-5p precursor and is involved in epithelial-to-mesenchymal transition (EMT). Transforming growth factor-β1 (TGF-β1) induces EMT in prostate cancer (PCa) by binding to TGF-beta receptor 2 (TGFBR2) to activate TGF-β signaling. However, the relationship between TGFBR2, E2F1, and miR-20b-5p in the modulation of EMT in PCa cells remains unknown. In this study, we found that the level of miR-20b-5p expression was significantly lower in PC3 and DU145 cells than that in prostate epithelial (RWPE-1) cells, and TGF-β1 treatment further down-regulated miR-20b-5p expression in these two cell lines. Functional studies showed that miR-20b-5p suppressed TGF-β1-induced migration and invasion of PC3 and DU145 cells by up-regulating E-cadherin and down-regulating vimentin, leading to TGF-β1-induced inhibition of EMT. Using gain and loss of function experiments, it was shown that E2F1 mediated TGF-β1 regulation of miR-20b-5p expression. Further, a luciferase activity assay showed that TGFBR2 was a direct target of miR-20b-5p in PCa cells. These results suggest that miR-20b-5p, TGFBR2, and E2F1 form a regulatory loop to modulate EMT induced by TGF-β1. A novel regulatory mechanism underlying the miR-20b-5p/TGFBR2/E2F1 axis is involved in TGF-β1-induced EMT of PCa cells, and miR-20b-5p may be a potential therapeutic target for PCa.

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Section: Introductionmentioning

confidence: 99%

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

Yang

Zhang

et al. 2020

Front. Oncol.

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“…At present, radiation, surgery or pharmacological androgen deprivation therapy is the most common treatments against PCa, especially for hormone-dependent PCa (HDPC). Although many PCa patients have HDPC, unfortunately, the vast majority of them finally become hormonal refractory PCa (HRPC) or castration-resistant PCa (CRPC) patients after 18 to 24 months [1, 2]. CRPC has become one of the difficult problems for urologists and oncologists due to its high metastatic potential, resistance to chemotherapeutic agents and easy relapse.…”

Section: Introductionmentioning

confidence: 99%

Corosolic acid, a natural triterpenoid, induces ER stress-dependent apoptosis in human castration resistant prostate cancer cells via activation of IRE-1/JNK, PERK/CHOP and TRIB3

Zhang

Wang

et al. 2018

J Exp Clin Cancer Res

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BackgroundThe development of potent non-toxic chemotherapeutic drugs against castration resistant prostate cancer (CRPC) remains a major challenge. Corosolic acid (CA), a natural triterpenoid, has anti-cancer activity with limited side effects. However, CA anti-prostate cancer activities and mechanisms, particularly in CRPC, are not clearly understood. In this study, we investigated CA anti-tumor ability against human CRPC and its mechanism of action.MethodsThe cell apoptosis and proliferation effects were evaluated via MTT detection, colony formation assay and flow cytometry. Western blot, gene transfection and immunofluorescence assay were applied to investigate related protein expression of Endoplasmic reticulum stress. A xenograft tumor model was established to investigate the inhibitory effect of CA on castration resistant prostate cancer in vivo.ResultsThe results showed that CA inhibited cell growth and induced apoptosis in human prostate cancer cell (PCa) line PC-3 and DU145, as well as retarded tumor growth in a xenograft model, exerting a limited toxicity to normal cells and tissues. Importantly, CA activated endoplasmic reticulum (ER) stress-associated two pro-apoptotic signaling pathways, as evidenced by increased protein levels of typical ER stress markers including IRE-1/ASK1/JNK and PERK/eIF2α/ATF4/CHOP. IRE-1, PERK or CHOP knockdown partially attenuated CA cytotoxicity against PCa cells. Meanwhile, CHOP induced expression increased Tribbles 3 (TRIB3) level, which lead to AKT inactivation and PCa cell death. CHOP silencing resulted in PCa cells sensitive to CA-induced apoptosis.ConclusionOur data demonstrated, for the first time, that CA might represent a novel drug candidate for the development of an anti-CRPC therapy.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0889-x) contains supplementary material, which is available to authorized users.

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“…The main aims of treatment for mCRPC are to delay progression, ameliorate symptoms and maintain or improve quality of survival. From a patient's perspective, optimal treatment is a trade-off between efficacy and tolerability, and while the increasing number of therapeutic options is welcome, a review of mCRPC clinical trial publications noted that Patient Reported Outcomes (PROs) were either not measured routinely or failed to be reported adequately hampering evaluation [8]. Those with good PRO data showed that enzalutamide compared with placebo significantly improved Quality of Life (QoL) in the AFFIRM trial [9], and in the PREVAIL trial was associated with a reduced risk of and delayed time to QoL deterioration, pain progression and occurrence of Serious Reportable Events (SREs) [10].…”

Section: Introductionmentioning

confidence: 99%

Treatment Experiences, Information Needs, Pain and Quality of Life in Men with Metastatic Castrate-resistant Prostate Cancer: Results from the EXTREQOL Study

et al. 2019

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Delaying progression, ameliorating symptoms and maintaining Quality of Life (QoL) are primary aims of treatment for metastatic Castrate Resistant Prostate Cancer (mCRPC). Real world rather than clinical trial data about symptoms and side effects are sparse. In EXTREQOL patients' QoL, pain and information needs were recorded during treatment. Methods Men with mCRPC from 20 UK cancer centres commencing various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months. Results 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate (FACT-P) mean=-3.89, 95% CI:-6.7 to-1.05, p =0.007; Trial Outcome Index analysis (TOI) mean=-3.10, 95% CI:-5.34 to-0.83, p = 0.007. Those who came off novel therapy and remained on LHRH agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale (PSC) mean difference=-4.45, 95% CI: 95%

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Patient-reported outcomes in metastatic castration-resistant prostate cancer

Cited by 30 publications

References 46 publications

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

miR-20b-5p, TGFBR2, and E2F1 Form a Regulatory Loop to Participate in Epithelial to Mesenchymal Transition in Prostate Cancer

Corosolic acid, a natural triterpenoid, induces ER stress-dependent apoptosis in human castration resistant prostate cancer cells via activation of IRE-1/JNK, PERK/CHOP and TRIB3

Treatment Experiences, Information Needs, Pain and Quality of Life in Men with Metastatic Castrate-resistant Prostate Cancer: Results from the EXTREQOL Study

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