Current opinion and mechanistic interpretation of combination therapy for castration-resistant prostate cancer

Xu, Jin; Qiu, Yun

doi:10.4103/aja.aja_10_19

Cited by 19 publications

(14 citation statements)

References 106 publications

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“…Adding specific anti-androgen inhibitors to taxane treatment may combat the influence of AR signaling on resistance. Specifically, enzalutamide is an FDA-approved nonsteroidal AR inhibitor that blocks the binding of AR to androgens in the cytoplasm and has been used alone, with ADT, with taxanes, or with the CYP17A inhibitor abiraterone [ 298 , 363 , 364 , 365 , 366 ]. Preliminary research showed that enzalutamide following taxane treatment increases progression-free survival and clinical trials are investigating the effects of DTX and enzalutamide combination therapy [ 363 , 364 , 367 , 368 ].…”

Section: Taxane Resistance In Prostate Cancermentioning

confidence: 99%

“…Specifically, enzalutamide is an FDA-approved nonsteroidal AR inhibitor that blocks the binding of AR to androgens in the cytoplasm and has been used alone, with ADT, with taxanes, or with the CYP17A inhibitor abiraterone [ 298 , 363 , 364 , 365 , 366 ]. Preliminary research showed that enzalutamide following taxane treatment increases progression-free survival and clinical trials are investigating the effects of DTX and enzalutamide combination therapy [ 363 , 364 , 367 , 368 ]. Interestingly, a significant decrease in MDR1 activity was observed with enzalutamide treatment, to the point where DTX-resistant cells were re-sensitized to DTX [ 322 ], suggesting an interaction between AR and efflux pumps that could prove useful for taxane-resistant cells.…”

Section: Taxane Resistance In Prostate Cancermentioning

confidence: 99%

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Mechanisms of Taxane Resistance

Maloney

Hoover

Morejon-Lasso

et al. 2020

Cancers

126

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The taxane family of chemotherapy drugs has been used to treat a variety of mostly epithelial-derived tumors and remain the first-line treatment for some cancers. Despite the improved survival time and reduction of tumor size observed in some patients, many have no response to the drugs or develop resistance over time. Taxane resistance is multi-faceted and involves multiple pathways in proliferation, apoptosis, metabolism, and the transport of foreign substances. In this review, we dive deeper into hypothesized resistance mechanisms from research during the last decade, with a focus on the cancer types that use taxanes as first-line treatment but frequently develop resistance to them. Furthermore, we will discuss current clinical inhibitors and those yet to be approved that target key pathways or proteins and aim to reverse resistance in combination with taxanes or individually. Lastly, we will highlight taxane response biomarkers, specific genes with monitored expression and correlated with response to taxanes, mentioning those currently being used and those that should be adopted. The future directions of taxanes involve more personalized approaches to treatment by tailoring drug–inhibitor combinations or alternatives depending on levels of resistance biomarkers. We hope that this review will identify gaps in knowledge surrounding taxane resistance that future research or clinical trials can overcome.

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Section: Taxane Resistance In Prostate Cancermentioning

confidence: 99%

Section: Taxane Resistance In Prostate Cancermentioning

confidence: 99%

Mechanisms of Taxane Resistance

Maloney

Hoover

Morejon-Lasso

et al. 2020

Cancers

126

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“…Clinical research studies have investigated the genomic biomarkers of docetaxel monotherapy; however, combination therapies with distinct mechanisms of action represent a more effective strategy. Combination therapies are thought to exert cancer-killing functions through either concomitant targeting of multiple pro-cancer factors or more effective inhibition of a single pathway [17]. The exact mechanisms by which these combinations can overcome drug resistance have yet to be fully understood [17].…”

Section: Germline Genomic Biomarkers In Research Studies For Prostmentioning

confidence: 99%

“…Combination therapies are thought to exert cancer-killing functions through either concomitant targeting of multiple pro-cancer factors or more effective inhibition of a single pathway [17]. The exact mechanisms by which these combinations can overcome drug resistance have yet to be fully understood [17].…”

Section: Germline Genomic Biomarkers In Research Studies For Prostmentioning

confidence: 99%

Pharmacogenomic Biomarkers in Docetaxel Treatment of Prostate Cancer: From Discovery to Implementation

Varnai

Koskinen

Mäntylä

et al. 2019

Genes

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Prostate cancer is the fifth leading cause of male cancer death worldwide. Although docetaxel chemotherapy has been used for more than fifteen years to treat metastatic castration resistant prostate cancer, the high inter-individual variability of treatment efficacy and toxicity is still not well understood. Since prostate cancer has a high heritability, inherited biomarkers of the genomic signature may be appropriate tools to guide treatment. In this review, we provide an extensive overview and discuss the current state of the art of pharmacogenomic biomarkers modulating docetaxel treatment of prostate cancer. This includes (1) research studies with a focus on germline genomic biomarkers, (2) clinical trials including a range of genetic signatures, and (3) their implementation in treatment guidelines. Based on this work, we suggest that one of the most promising approaches to improve clinical predictive capacity of pharmacogenomic biomarkers in docetaxel treatment of prostate cancer is the use of compound, multigene pharmacogenomic panels defined by specific clinical outcome measures. In conclusion, we discuss the challenges of integrating prostate cancer pharmacogenomic biomarkers into the clinic and the strategies that can be employed to allow a more comprehensive, evidence-based approach to facilitate their clinical integration. Expanding the integration of pharmacogenetic markers in prostate cancer treatment procedures will enhance precision medicine and ultimately improve patient outcomes.

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“…Due to the limited efficacy and side effects of monotherapy, effective combination therapies or novel treatment regimens still need to be developed to obtain better efficacy outcomes. 5 Recently, a growing interest has been attracted to such novel treatments as immunotherapy 6 and PTT therapy. 7 However, few available studies can offer guidance to whether and how to combine these modalities, and their synergistic applications may give another perspective in the treatment of PCa.…”

Section: Introductionmentioning

confidence: 99%

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

Lin¹,

Li²,

Xu³

et al. 2021

IJN

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Purpose With the advance of screening techniques, there is a growing number of low-risk or intermediate-risk prostate cancer (PCa) cases, remaining a serious threat to men’s health. To obtain better efficacy, a growing interest has been attracted to develop such emerging treatments as immunotherapy and focal therapy. However, few studies offer guidance on whether and how to combine these modalities against PCa. This study was designed to develop dual-functional nanoparticles (NPs) which combined photothermal therapy (PTT) with immunotherapy and determine the anti-tumor efficacy for PCa treatment. Methods By a double emulsion technique, the drug nanocarrier, poly(lactic-co-glycolic acid) or PLGA, was applied for co-loading of a fluorescent dye, indocyanine green (ICG) and a toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) to synthesize PLGA-ICG-R848 NPs. Next, we determined their characteristic features and evaluated whether they inhibited the cell viability in multiple PCa cell lines. After treatment with PLGA-ICG-R848, the maturation markers of bone marrow-derived dendritic cells (BMDCs) were detected by flow cytometry. By establishing a subcutaneous xenograft model of mouse PCa, we explored both the anti-tumor effect and immune response following the NPs-based laser ablation. Results With a mean diameter of 157.7 nm, PLGA-ICG-R848 exhibited no cytotoxic effect in PCa cells, but they significantly decreased RM9 cell viability to (3.9±1.0)% after laser irradiation. Moreover, PLGA-ICG-R848 promoted BMDCs maturation with the significantly elevated proportions of CD11c+CD86+ and CD11c+CD80+ cells. Following PLGA-ICG-R848-based laser ablation in vivo, the decreased bioluminescent signals indicated a significant inhibition of PCa growth, while the ratio of splenic natural killer (NK) cells in PLGA-ICG-R848 was (3.96±1.88)% compared with (0.99±0.10)% in PBS group, revealing the enhanced immune response against PCa. Conclusion The dual-functional PLGA-ICG-R848 NPs under laser irradiation exhibit the anti-tumor efficacy for PCa treatment by combining PTT with immunotherapy.

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Current opinion and mechanistic interpretation of combination therapy for castration-resistant prostate cancer

Cited by 19 publications

References 106 publications

Mechanisms of Taxane Resistance

Mechanisms of Taxane Resistance

Pharmacogenomic Biomarkers in Docetaxel Treatment of Prostate Cancer: From Discovery to Implementation

Dual-Functional PLGA Nanoparticles Co-Loaded with Indocyanine Green and Resiquimod for Prostate Cancer Treatment

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