Medical strategies for treatment of castration resistant prostate cancer (CRPC) docetaxel resistant

Altavilla, Amelia; Iacovelli, Roberto; Procopio, Giuseppe; Adami, Daniele; Risi, Emanuela; Campennì, Giuseppe; Palazzo, Antonella; Cortesi, Enrico

doi:10.4161/cbt.21188

Cited by 7 publications

(7 citation statements)

References 52 publications

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“…Despite an early response to ADT, the majority of patients generally develop castration-resistant prostate cancers (CRPC) within few years. Despite docetaxel (taxotere)-based chemotherapy confers a survival benefit in CRPC patients, 3 median overall survival (OS) for patients affected by metastatic CRPC is less than 20 months supporting the need to identify events crucial in tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Combined targeting of EGFR and HER2 against prostate cancer stem cells

Rossini

Giussani

Ripamonti

et al. 2020

Cancer Biology & Therapy

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Progression of prostate cancer has been associated with EGFR and HER2 activation and to tumorinitiating cells contribution toward chemotherapy resistance. We investigated the efficacy of a dual intervention against EGFR and HER2 to deplete the tumor-initiating cells, optimize the chemotherapy management and prevent the progression of castration-resistant prostate cancer (CRPC) cells. Using DU145, PC3, and 22Rv1 CRPC cell lines, biochemical analysis revealed activation of EGFR, HER2, MAPK, and STAT3 in DU145 and 22Rv1, and AKT and SRC in DU145 and PC-3. pSTAT3 nuclear staining was observed in DU145 xenografts and in 12 out of 14 CRPC specimens. The in vivo dual targeting of ErbB receptors with Cetuximab and Trastuzumab combined with chemotherapy caused an effective antitumor response in DU145 xenografted mice displaying STAT3 activation; conversely PC-3 bearing mice experienced tumor relapse. The potentiating of in vivo cytotoxic effect in DU145 model was accompanied by a significant decrease of prostatosphere-forming capacity assessed in vitro on residual tumor cells. Additionally, combined treatment in vitro with Cetuximab, Trastuzumab and chemotherapy negatively affected DU145 and 22Rv1 sphere formation, suggesting the critical function of ErbB receptors for tumor-initiating cells proliferation; no effect on PC-3 clonogenic potential was observed, indicating that other receptors than EGFR and HER2 may sustain PC3 tumor-initiating cells. These findings provided the preclinical evidence that the dual inhibition of EGFR and HER2 by targeting tumorinitiating cells may improve the efficacy of the current chemotherapy regimen, bringing benefits especially to castration-resistant patients with activated STAT3, and preventing disease progression.

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Section: Introductionmentioning

confidence: 99%

Combined targeting of EGFR and HER2 against prostate cancer stem cells

Rossini

Giussani

Ripamonti

et al. 2020

Cancer Biology & Therapy

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“…Recently, a large phase III trial confirmed the activity and safety of ABI in CRPC patients untreated with docetaxel. 4 This study (COU-AA-302) reports as CHT naïve CRPC patients have a similar benefit from ABI compared with post-CHT one in terms of radiographic progression-free survival (HRs: 0.67 vs 0.69, respectively) and control of disease (16.5 vs 5.6 months), but no patients with PS-2 were enrolled. 26,27 Our data may suggest such as the increased survival found in PS-0/1 patients may be also reached in poor PS patients even in pre-docetaxel setting, considering that recent analysis reported as ABI and ENZ are able to reduce pain, fatigue and skeletal related events in CRPC patients.…”

Section: Discussionmentioning

confidence: 97%

“…About prostate cancer, current guidelines do not report the best sequence of therapy after docetaxel failure, and several algorithms have been proposed in medical literature. 4,25 In registration trials, the incidence of high-grade adverse events was quite similar in the three drugs (55% for abiraterone, 57% for CBZ and 45% for ENZ), [19][20][21] but with a different toxicity profile for each one. In fact, CBZ is mainly characterized by hematologic toxicity (neutropenia G3-4 in 82% and anemia G3-4 in 11% of cases) and ABI by cardiovascular toxicity (5% of patients for grade 3 or 4).…”

Section: Discussionmentioning

confidence: 99%

“…2,3 In recent years, several agents have reported to increase survival, delay disease progression and improve quality of life after docetaxel progression. 4 About 20% of patients with a new diagnosis of prostate cancer have an ECOG performance status (PS) X2, and the portion is probably higher in patients with advanced disease. 5 Furthermore, PS and other factors such as baseline value of hemoglobin under the lower normal limit, weight loss and pain have been related to a short survival in patients with hormone sensitive and CRPC.…”

Section: Introductionmentioning

confidence: 99%

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Are post-docetaxel treatments effective in patients with castration-resistant prostate cancer and performance of 2? A meta-analysis of published trials

Iacovelli

Altavilla

Procopio

et al. 2013

Prostate Cancer Prostatic Dis

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“…Although the last decade has resulted in a handful of new approved drugs, i.e. drugs that improve the overall survival time for CRPC patients (10)(11)(12)(13)(14), there is an unmet need for new drugs with a positive impact on survival and quality of life. Quality of life is intimately related with side- effects of the drugs that are used for treating the CRPC patient.…”

Section: Discussionmentioning

confidence: 99%