The Emerging Role of Immunotherapy in Castrate-Resistant Prostate Cancer

While androgen-targeted therapies are routinely used in advanced prostate cancer (PCa), their effect is poorly understood in treating bone metastatic lesions and ultimately results in the development of metastatic castrate resistant prostate cancer (mCRPC). Here, we used an all-human microtissue-engineered model of mineralized metastatic tissue combining human osteoprogenitor cells, 3D printing and prostate cancer cells, to assess the effects of the antiandrogens, bicalutamide, and enzalutamide in this microenvironment. We demonstrate that cancer/bone stroma interactions and antiandrogens drive cancer progression in a mineralized microenvironment. Probing the bone microenvironment with enzalutamide led to stronger cancer cell adaptive responses and osteomimicry than bicalutamide. Enzalutamide presented with better treatment response, in line with enzalutamide delaying time to bone-related events and enzalutamide extending survival in mCRPC. The all-human microtissue-engineered model of mineralized metastatic tissue presented here represents a substantial advance to dissect the role of the bone tumor microenvironment and responses to therapies for mCPRC.

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Liquid Biopsies in Castrate-Resistant Prostate Cancer: Future Prospects in Radiation Oncology

10.47890/jcrat/2020/gcarlos/18041702 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Carlos Galvis ◽

María Caicedo Martinez

Keyword(s):

Prostate Cancer ◽

Radiation Oncology ◽

Liquid Biopsies ◽

Castrate Resistant Prostate Cancer ◽

Pre Treatment ◽

Castrate Resistant ◽

Molecular Patterns ◽

Available Information

The use of liquid biopsies, based on circulating tumor cells and tumoral DNA, provides information on the molecular patterns and genomics of Castrate-Resistant Prostate Cancer. There is evidence on the role of the androgen receptor variant 7 as a prognostic and as a follow-up tool, especially as a follow-up to treatment response and resistance with Enzalutamide and Abiraterone. Little is known about the genomics of Castrate Resistant Prostate Cancer and its relationship to radiation therapy’s sensibility. This is particularly relevant for patients with oligometastatic disease, who could obtain a long control of the disease with radiation. In this narrative review, we summarize the available information on liquid biopsies and Castrate Resistant Prostate Cancer. As radiation oncology evolves towards Genomically Adapted Radiation Dose, the role of liquid biopsies as a possible pre-treatment assessment is a future target. Nonetheless, models have been modeled after other malignancies. This highlights the need for further studies to assess the use of personalized medicine in these patients. Keywords: Radiotherapy; Prostate Cancer; Receptors Androgen; Liquid Biopsy; Precision Medicine;

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Potential role of rituximab in metastatic castrate-resistant prostate cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155218790338 ◽

2018 ◽

Vol 25 (6) ◽

pp. 1509-1511 ◽

Cited By ~ 4

Author(s):

Poorva Bindal ◽

Sharif AA Jalil ◽

Lisa M Holle ◽

Jessica M Clement

Keyword(s):

Prostate Cancer ◽

B Cell ◽

Disease Progression ◽

Androgen Deprivation ◽

Cell Infiltration ◽

Prostate Cells ◽

Develop Disease Progression ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.

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Comparison of survival of African-American (AA) patients (pts) in docetaxel (D)-based combination therapies in metastatic castrate-resistant prostate cancer (mCRPC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.272 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 272-272

Author(s):

Fatima Karzai ◽

Ravi Amrit Madan ◽

Yang-Min Ning ◽

Marc Robert Theoret ◽

Philip M. Arlen ◽

...

Keyword(s):

Prostate Cancer ◽

Specific Antigen ◽

Progression Free Survival ◽

Median Number ◽

Incidence And Mortality ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant ◽

Number Of Cycles ◽

Ecog Ps

272 Background: AA pts experience greater prostate cancer (PC) incidence and mortality compared to Caucasian (C) pts but are underrepresented in clinical trials (CTs). Greater representation of AAs is required to explore differences in clinical benefit in advanced disease where recent data has reaffirmed the role of D. Methods: In a retrospective analysis, baseline characteristics, Gleason score (GS), ECOG PS, number of cycles (cys), maximum prostate-specific antigen (PSA) declines, radiographic responses, overall survival (OS) and progression-free survival (PFS) were captured in 2 recent D based CTs. Results: Of 136 pts, 28 (21%) self-identified as Black or AA. Median age of AA pts is 66 (50-78 yrs). Median GS is 8 (5-10). Median ECOG PS is 1 (0-2). 15 pts have bone and soft tissue disease; 13 pts have bone only disease. Median number of cys is 28.5 (1-63). Of 27 evaluable pts, 26 had PSA declines (-26 to -99%). Radiographic responses include 11 (39%) partial responses and 16 (57%) pts with stable disease. Median OS for AAs is 29.0 months (mos) (95% CI: 20.9-34.7 mos); median PFS is 21.5 mos (95% CI: 13.7-28.9 mos). Median OS for all non-AA pts is 24.8 mos (95% CI: 21.8-29.5 mos); median PFS is 16.1 mos (95% CI: 14.1-20.1 mos). The VEGF-634G > C SNP, associated with a more aggressive phenotype of PC, was evaluated in 54 pts. No evidence was found that genotype frequency varies between C and AA pts. Conclusions: In this analysis, AA pts did not have inferior OS (29 mos) or PFS (21.5 mos) outcomes compared to non-AA pts (24.8, 16.1 mos). Further analysis from larger studies is required to determine differential benefits of D for AA pts compared to non-AA pts. Clinical trial information: NCT00089609, NCT00942578.

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