Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer

Reuter, Christoph; Morgan, Michael; Ivanyi, Philipp; Fenner, Martin; Ganser, Arnold; Grünwald, Viktor

doi:10.1007/s00345-010-0527-5

Cited by 18 publications

(4 citation statements)

References 29 publications

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“…The response to DTX is, however, partial and associated with increased resistance to apoptosis, thus indicating a clear need for new therapies in HRPC patients. Recent report shows that single-agent satraplatin or carboplatin improves PFS as second-line chemotherapy for patients with HRPC (Nakabayashi et al 2008, Reuter et al 2010. Repopulation during courses of chemotherapy is an important cause of drug resistance in patients.…”

Section: Discussionmentioning

confidence: 99%

The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells

Gravina

Marampon²,

Petini³

et al. 2011

Endocrine-Related Cancer

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One of the major obstacles in the treatment of hormone-refractory prostate cancer (HRPC) is the development of chemo-resistant tumors. The aim of this study is to evaluate the role of Palomid 529 (P529), a novel TORC1/TORC2 inhibitor, in association with docetaxel (DTX) and cisplatin (CP). This work utilizes a wide panel of prostatic cancer cell lines with or without basal activation of Akt as well as two in vivo models of aggressive HRPC. The blockade of Akt/mTOR activity was associated to reduced cell proliferation and induction of apoptosis. Comparison of IC50 values calculated for PTEN-positive and PTEN-negative cell lines as well as the PTEN transfection in PC3 cells or PTEN silencing in DU145 cells revealed that absence of PTEN was indicative for a better activity of the drug. In addition, P529 synergized with DTX and CP. The strongest synergism was achieved when prostate cancer (PCa) cells were sequentially exposed to CP or DTX followed by treatment with P529. Treatment with P529 before the exposure to chemotherapeutic drugs resulted in a moderate synergism, whereas intermediated values of combination index were found when drugs were administered simultaneously. In vivo treatment of a combination of P529 with DTX or CP increased the percentage of complete responses and reduced the number of mice with tumor progression. Our results provide a rationale for combinatorial treatment using conventional chemotherapy and a Akt/mTOR inhibitor as promising therapeutic approach for the treatment of HRPC, a disease largely resistant to conventional therapies.

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Section: Discussionmentioning

confidence: 99%

The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells

Gravina

Marampon²,

Petini³

et al. 2011

Endocrine-Related Cancer

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“…However, Doc resistance has already become one of the clinical problems. Clinically, about 50% of patients poorly responded to Doc treatment and patients who initially responded it well would eventually develop resistance phenotype [6, 11, 12]. Therefore, understanding the development of Doc resistance and finding novel therapy to overcome it become major scientific and clinical interests.…”

Section: Introductionmentioning

confidence: 99%

Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells

Qiu

Wang

et al. 2019

BMC Cancer

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BackgroundDocetaxel was used to treat metastatic CRPC patients. However, Doc resistance in prostate cancer (PCa) hinders its clinical application.ObjectiveTo understand the underlying mechanisms by which Doc resistance is developed and to find novel therapeutic target to cure Doc resistant PCa has clinical importance.MethodsWe established Doc resistant cell lines and explored the role of Ezh2 in the development of Doc resistance by overexpressing its cDNA or using its inhibitor.ResultsWe found that Ezh2 was induced in our established Doc resistant (DocR) cells, which was attributable to the silenced expression of miR-101-3p and miR-138-5p. Blockage of Ezh2 activity by either inhibitor or miRNA mimics could overcome Doc resistance by suppressing Doc-induced cancer stem cells populations. Mechanistically, Ezh2 activity was required for the induced expression of Nanog, Sox2 and CD44 upon Doc treatment.ConclusionsTargeting Ezh2 could overcome Doc resistance.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-5228-2) contains supplementary material, which is available to authorized users.

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“…However, many clinical trials of second line chemotherapy have been disappointing, as Colloca et al (4) summarize in their review of taxane-based and non-taxane-based chemotherapy for docetaxel-resistant CRPC patients. The taxane-based chemotherapy includes carboplatin plus docetaxel or estramustine plus docetaxel (5)(6)(7)(8), and non-taxane-based chemotherapy includes calcitriol plus docetaxel (9) or replacing docetaxel with mitoxantrone (10, 11) and prednisone (12). However, none of them showed satisfactory results.…”

mentioning

confidence: 99%

Increased Chemosensitivity via Targeting Testicular Nuclear Receptor 4 (TR4)-Oct4-Interleukin 1 Receptor Antagonist (IL1Ra) Axis in Prostate Cancer CD133+ Stem/Progenitor Cells to Battle Prostate Cancer

Yang

Ding

Luo

et al. 2013

Journal of Biological Chemistry

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Background: PCa stem/progenitor cells develop higher chemoresistance. Results: High TR4 levels in PCa stem/progenitor cells were shown to be critical in conferring chemoresistance to these cells. Conclusion: TR4-Oct4-IL1Ra signaling is important in conferring chemoresistance to PCa stem/progenitor cells. Significance: This finding suggests that targeting TR4 and its downstream molecules may be a better therapeutic approach to battle PCa stem/progenitor cell-originated chemoresistance.

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Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer

Abstract: These data suggest that weekly docetaxel plus carboplatin may be an important therapeutic second-line treatment option for patients with DRPC.

Cited by 18 publications

References 29 publications

The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells

The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells

Targeting Ezh2 could overcome docetaxel resistance in prostate cancer cells

Increased Chemosensitivity via Targeting Testicular Nuclear Receptor 4 (TR4)-Oct4-Interleukin 1 Receptor Antagonist (IL1Ra) Axis in Prostate Cancer CD133+ Stem/Progenitor Cells to Battle Prostate Cancer

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