Cabazitaxel in the treatment of metastatic castration-resistant prostate cancer: patient selection and special considerations

Patel, Sheel; Hoffman-Censits, Jean H.

doi:10.2147/ott.s103532

Cited by 9 publications

(3 citation statements)

References 31 publications

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“…Current agents approved by the US Food and Drug Administration (FDA) that have shown efficacy in terms of overall survival (OS) in patients with mCRPC include docetaxel, cabazitaxel, radium-223, sipuleucel-T, and androgen receptor axis-targeted agents including abiraterone and enzalutamide [3][4][5][6][7][8]. Since the approval of sipuleucel-T in 2010 [4], there have been significant advancements and innovations in the field of immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Current Status and Future Perspectives of Checkpoint Inhibitor Immunotherapy for Prostate Cancer: A Comprehensive Review

Kim

Koo

2020

IJMS

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The clinical spectrum of prostate cancer (PCa) varies from castration-naive to metastatic castration-resistant disease. Despite the administration of androgen synthesis inhibitors and chemotherapy regimens for castration-resistant prostate cancer, the treatment options for this entity are limited. The utilization of the immune system against cancer cells shows potential as a therapeutic modality for various solid tumors and hematologic malignancies. With technological advances over the last decade, immunotherapy has become an integral treatment modality for advanced solid tumors. The feasibility of immunotherapy has shown promise for patients with PCa, and with advances in molecular diagnostic platforms and our understanding of immune mechanisms, immunotherapy is reemerging as a potential treatment modality for PCa. Various combinations of individualized immunotherapy and immune checkpoint blockers with androgen receptor-targeted therapies and conventional cytotoxic agents show promise. This article will review the current status of immunotherapy, including new discoveries and precision approaches to PCa, and discuss future directions in the continuously evolving landscape of immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Current Status and Future Perspectives of Checkpoint Inhibitor Immunotherapy for Prostate Cancer: A Comprehensive Review

Kim

Koo

2020

IJMS

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“…Taxanes are microtubule stabilizers that inhibit disassembly of microtubules to render cells in mitotic arrest and further prevent further cell division and growth [ 14 , 15 ]. Docetaxel (DTX) and cabazitaxel (CBZ) are the two chemotherapies approved to treat metastatic castration-resistant prostate cancer (mCRPC) [ 14 , 16 ]. These chemotherapies have helped extend patient survival by several months; however, chemoresistance inevitably ensues and patients are left with limited treatment options leading to tumor progression, recurrence, and metastasis [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Overcoming TRAIL-resistance by sensitizing prostate cancer 3D spheroids with taxanes

et al. 2021

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Three-dimensional spheroid cultures have been shown to better physiologically mimic the cell-cell and cell-matrix interactions that occur in solid tumors more than traditional 2D cell cultures. One challenge in spheroid production is forming and maintaining spheroids of uniform size. Here, we developed uniform, high-throughput, multicellular spheroids that self-assemble using microwell plates. DU145 and PC3 cells were cultured as 2D monolayers and 3D spheroids to compare sensitization of TRAIL-resistance cancer cells to TRAIL mediated apoptosis via chemotherapy based on dimensionality. Monocultured monolayers and spheroids were treated with soluble TRAIL alone (24 hr), DTX or CBZ alone (24 hr), or a combination of taxane and TRAIL (24 + 24 hr) to determine the effectiveness of taxanes as TRAIL sensitizers. Upon treatment with soluble TRAIL or taxanes solely, monolayer cells and spheroids exhibited no significant reduction in cell viability compared to the control, indicating that both cell lines are resistant to TRAIL and taxane alone in 2D and 3D. Pretreatment with CBZ or DTX followed by TRAIL synergistically amplified apoptosis in 2D and 3D DU145 cell cultures. PC3 spheroids were more resistant to the combination therapy, displaying a more additive effect in the DTX + TRAIL group compared to 2D. There was a downregulation of DR4/5 expression in spheroid form compared to monolayers in each cell line. Additionally, normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were cocultured with both PCa cell lines as spheroids to determine if CAFs confer additional resistance to chemotherapy. We determined that co-cultured spheroids show similar drug resistance to monocultured spheroids when treated with taxane plus TRAIL treatment. Collectively, these findings suggest how the third dimension and cocultures of different cell types effect the sensitization of androgen-independent prostate cancer cells to TRAIL, suggesting therapeutic targets that could overcome TRAIL-resistance in metastatic castration-resistant prostate cancer (mCRPC).

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“…PCa patients respond to androgen deprivation therapy (ADT) initially but almost all patients progress to metastatic castration-resistant prostate cancer (mCRPC) [3]. Food and Drug Administration (FDA) approved chemotherapy treatments for mCRPC, docetaxel and cabazitaxel, in combination with enzalutamide, abiraterone and Sipuleucel-T (Sip-T dendritic cell vaccine) [4][5][6][7][8][9], only increase median survival benefit by 2-4 months [10,11]. Other therapies are therefore being explored to treat mCRPC patients, and one of the most promising ones is immunotherapy with immune check point inhibitors (ICIs).…”

Section: Introductionmentioning

confidence: 99%

Immune Checkpoint Inhibitors Therapy in Prostate Cancer: Lessons Learnt

Naamoune¹

2020

AII

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Immune checkpoint inhibitors (ICIs) therapy has rapidly changed the treatment landscape for a number of cancers but resulted in only marginal success in prostate cancer (PCa). In order to bring about durable clinical benefit of immune check point inhibitor therapy in prostate cancer, it is critical to understand the current status of ICIs therapy for PCa and reasons for low/negligible outcomes. This article summarizes the current status of ICIs therapy in PCa and discusses how ICIs therapy can result in the successful treatment of a specific subset of PCa patients. In this article, we review how immunotherapy and different combination therapies are paving their way by incorporating the strategies of converting the “cold” PCa tumor into “hot”, role of genomic landscape of PCa in influencing the outcome of ICIs therapy, what are the promising novel biomarker candidates, which can guide the patient selection for ICIs therapy and help in monitoring the efficacy of treatment. This article highlights that ICIs therapy hold a promising future in subset of PCa patients.

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Cabazitaxel in the treatment of metastatic castration-resistant prostate cancer: patient selection and special considerations

Cited by 9 publications

References 31 publications

Current Status and Future Perspectives of Checkpoint Inhibitor Immunotherapy for Prostate Cancer: A Comprehensive Review

Current Status and Future Perspectives of Checkpoint Inhibitor Immunotherapy for Prostate Cancer: A Comprehensive Review

Overcoming TRAIL-resistance by sensitizing prostate cancer 3D spheroids with taxanes

Immune Checkpoint Inhibitors Therapy in Prostate Cancer: Lessons Learnt

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