Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

Tagawa, Scott T.; Beltran, Himisha

doi:10.1038/aja.2011.113

Cited by 3 publications

(1 citation statement)

References 21 publications

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“…Despite an initial response to ADT in ~80% of patients 4 , relapse and progression to castration-resistant prostate cancer (CRPC) are often inevitable. Interestingly, CRPC tumors retain a high level of AR signaling 5 , thus allowing CRPC patients to benefit from more potent second-generation AR targeting by androgen receptor-signaling inhibitors (ARSIs) 6 – 11 , with Enzalutamide (Enza) as one of the most commonly used ARSIs 9 .…”

Section: Introductionmentioning

confidence: 99%

Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC

Panja,

Truica,

et al. 2024

Nat Commun

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Heterogeneous response to Enzalutamide, a second-generation androgen receptor signaling inhibitor, is a central problem in castration-resistant prostate cancer (CRPC) management. Genome-wide systems investigation of mechanisms that govern Enzalutamide resistance promise to elucidate markers of heterogeneous treatment response and salvage therapies for CRPC patients. Focusing on the de novo role of MYC as a marker of Enzalutamide resistance, here we reconstruct a CRPC-specific mechanism-centric regulatory network, connecting molecular pathways with their upstream transcriptional regulatory programs. Mining this network with signatures of Enzalutamide response identifies NME2 as an upstream regulatory partner of MYC in CRPC and demonstrates that NME2-MYC increased activities can predict patients at risk of resistance to Enzalutamide, independent of co-variates. Furthermore, our experimental investigations demonstrate that targeting MYC and its partner NME2 is beneficial in Enzalutamide-resistant conditions and could provide an effective strategy for patients at risk of Enzalutamide resistance and/or for patients who failed Enzalutamide treatment.

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Section: Introductionmentioning

confidence: 99%

Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC

Panja,

Truica,

et al. 2024

Nat Commun

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

Lin¹,

Yao²,

Ye³

et al. 2012

Asian J Androl

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We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer (mCRPC). In total, 163 patients with mCRPC were eligible, receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone. Progression-free survival (PFS) was calculated from the beginning of the ketoconazole therapy to the onset of disease progression. The prognostic value of different variables for PFS was assessed by Cox regression analysis. The median PFS was 2.6 months (0.5-8.6 months) for these patients. The serum testosterone level changed during therapy, which decreased when the prostate-specific antigen (PSA) declined; the serum testosterone level increased as the levels of PSA relapsed. The median PFS values for patients associated with different factors were the following: 1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and <0.2 ng ml(-1), respectively (hazard rate (HR)=4.767, P<0.001); 3.1 and 1.6 months for a baseline testosterone of ≥ 0.1 and <0.1 ng ml(-1), respectively (HR=2.865, P=0.012); 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and <120 g l(-1), respectively (HR=1.605, P<0.001); and 3.0 and 1.9 months for a PSA doubling time (PSADT) of ≥ 2.0 and <2.0 months, respectively (HR=1.454, P=0.017). A risk model was constructed according to the four factors that divided patients into three subgroups of low risk (0-1 factors), moderate risk (2 factors) and high risk (3-4 factors) with PFS values of 3.6, 3.0 and 1.4 months, respectively (HR=1.619, P<0.001). A nadir PSA of ≥ 0.2 ng ml(-1), a baseline testosterone of <0.1 ng ml(-1), a baseline haemoglobin of <120 g l(-1) and a PSADT of <2 months were associated with a poor PFS. This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.

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Current World Literature

2012

Current Opinion in Supportive &Amp; Palliative Care

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Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

Cited by 3 publications

References 21 publications

Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC

Mechanism-centric regulatory network identifies NME2 and MYC programs as markers of Enzalutamide resistance in CRPC

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

Current World Literature

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