Drug resistance in metastatic castration-resistant prostate cancer

  title={Drug resistance in metastatic castration-resistant prostate cancer},
  author={Bo{\vs}tjan {\vS}eruga and Alberto Oca{\~n}a and Ian F. Tannock},
  journal={Nature Reviews Clinical Oncology},
Docetaxel in combination with prednisone is the standard of care in men with symptomatic castration-resistant prostate cancer (CRPC). However, a substantial proportion of men with CRPC do not benefit from docetaxel or other systemic therapy and those who do benefit invariably progress and die of (or with) prostate cancer. Resistance to chemotherapy in metastatic CRPC is a result of cellular mechanisms of drug resistance intrinsic to prostate cancer and general mechanisms common to different… 

Emerging targets to monitor and overcome docetaxel resistance in castration resistant prostate cancer (review).

The molecules associated with resistance, such as the molecular chaperones heat shock proteins and clusterin, and the cytokines interleukin-6 (IL-6) and the divergent member of the tumor growth factor family MIC-1 (macrophage inhibitory cytokine-1 also named GDF-15) are discussed, and their interest as blood-based markers to monitor docetaxel resistance.

Current Treatment Modalities Targeting Tumor Microenvironment in Castration-Resistant Prostate Cancer.

The current state of the literature regarding treatment modalities is reviewed, focusing on the treatment recommendations per the American Urological Association (AUA), recent clinical trials, and their limitations.

Chemotherapy-based treatment for castration-resistant prostate cancer.

  • B. ŠerugaI. Tannock
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2011
With the approval of less toxic hormonal agents in the setting of docetaxel-resistant mCRPC, clinicians will have an opportunity to balance benefits and harms of new agents in an individual patient and may be able to use different agents in sequence.

Overcoming docetaxel resistance in prostate cancer: a perspective review

  • C. Hwang
  • Medicine, Biology
    Therapeutic advances in medical oncology
  • 2012
Recent therapeutic advances in metastatic castrate-resistant prostate cancer as well as ongoing clinical trials are discussed, including several new drugs that are effective after docetaxel failure, dramatically changing the therapeutic landscape for these patients.

Androgen Receptor Signaling in Castration Resistant Prostate Cancer

The mechanisms through which the AR signaling axis promotes resistance to androgen-deprivation therapy and drives progression of castration resistant prostate cancer (CRPC) are reviewed.

Novel therapeutic strategies for metastatic prostate cancer in the post-docetaxel setting.

The cell-based immunotherapy sipuleucel-T produces longer OS times in chemotherapy-naïve patients, whereas the androgen biosynthesis inhibitor abiraterone acetate results in longerOS times following docetaxel, envisioned that these agents will change the standard of care for patients with metastatic CRPC.

Overcoming Drug Resistance and Treating Advanced Prostate Cancer

This review will present recent findings on the molecular and cellular pathways that are responsible for bone metastasis of PCa, and address several novel mechanisms with a focus on the role of bone and bone marrow microenvironment in promoting PCa metastasis.

Treatment patterns and clinical efectiveness in metastatic castrate resistant prostate cancer after frst-line docetaxel

Patients with castrateresistant prostate cancer (mCRPC) who have a progression after docetaxel therapy may receive rechallenge with docetAXel or be considered for other subsequent therapies, as well as those patients who can tolerate taxane therapy.



Survivin mediates resistance to antiandrogen therapy in prostate cancer

The study indicates that upregulation of Survivin via IGF-1 signaling confers resistance to Flutamide in prostate cancer cells, supporting a novel mechanism of resistance to antiandrogen therapy.

Genomic strategy for targeting therapy in castration-resistant prostate cancer.

A transcription-based AR signature can detect AR activity within individual prostate cancer specimens and has the potential to help individualize and improve care for patients with castrate-resistant prostate cancer.

Second-line chemotherapy for advanced hormone-refractory prostate cancer.

The entirety of phase II and III data evaluating chemotherapy agents in second-line prostate cancer (HRPC) is reviewed.

A phase II trial of docetaxel and erlotinib as first-line therapy for elderly patients with androgen-independent prostate cancer

Docetaxel/erlotinib can be delivered safely in elderly patients with AIPC and anti-cancer disease activity appears generally comparable to docetaxe when used as monotherapy.

Maintenance of intratumoral androgens in metastatic prostate cancer: a mechanism for castration-resistant tumor growth.

Maximal therapeutic efficacy in the treatment of castration-resistant prostate cancer will require novel agents capable of inhibiting intracrine steroidogenic pathways within the prostate tumor microenvironment.

Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer.

  • Y. NingJ. Gulley W. Dahut
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
The addition of bevacizumab and thalidomide to docetaxel is a highly active combination with manageable toxicities, and the estimated median survival is encouraging, given the generally poor prognosis of this patient population.

A phase II trial of lapatinib in hormone refractory prostate cancer

Patients with rising PSA on androgen deprivation therapy who completed antiandrogen withdrawal, if previously on anti androgen, and have not received chemotherapy were eligible and were treated with lapatinib at an oral dose of 1500 mg daily.

Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemotherapy.

Sunitinib malate demonstrated promising activity in metastatic CRPC progressing after prior docetaxel, and was evaluated in patients with progressing metastaticCRPC following prior docentaxel.

Phase II multicenter study of abiraterone acetate plus prednisone therapy in patients with docetaxel-treated castration-resistant prostate cancer.

  • D. DanilaM. Morris H. Scher
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2010
This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy, with encouraging antitumor activity in heavily pretreated CRPC patients.

Prostate cancer stem cells: a new target for therapy.

  • N. MaitlandA. Collins
  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2008
The emergence of new stem-cell therapeutic targets not only will require new assays for efficacy (because of their relatively quiescent nature), but also holds real promise of more lasting treatments to augment those currently directed against the remaining tumor cells, which comprise 99.9% of tumor mass, but paradoxically have a poor tumor-initiating capacity.