Might Enzalutamide [Xtandi] sensitize PCa to radiation?

[pjoshea13]

New UK/Spanish cell study [1].

"A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade."

LNCaP & PC-3 (with DU145) are the standard cell lines used in PCa research. They are useful because of their properties, rather than being characteristic of real-life tumors. However, LNCaP was taken from a lymph node met & PC-3 from a bone met (DU145 was obtained from a brain met.) PC-3 cells do not respond to androgens & do not produce PSA. Also, they form osteolytic lesions, rather than osteoblastic. So most men will not have bone mets with those properties.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/308...

Rep Pract Oncol Radiother. 2019 Mar-Apr;24(2):221-226. doi: 10.1016/j.rpor.2019.02.002. Epub 2019 Feb 22.

Radiopotentiation of enzalutamide over human prostate cancer cells as assessed by real-time cell monitoring.

Barrado M1,2, Blanco-Luquin I1, Navarrete PA2, Visus I2, Guerrero-Setas D1, Escors D1,3, Kochan G1, Arias F2.

Author information

1

Biomedical Research Center of Navarra-Navarrabiomed, Fundación Miguel Servet, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarre, Spain.

2

Department of Radiation Oncology, Hospital of Navarre, IdISNA, Irunlarrea 3, 31008 Pamplona, Navarre, Spain.

3

Department of Infection and Immunity, Rayne Institute, University College London, 5 University Street, WC1E 6JJ London, United Kingdom.

Abstract

AIM:

To evaluate the radiopotentiation of enzalutamide in human prostate cancer cells.

BACKGROUND:

While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy.

MATERIALS AND METHODS:

Here, we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real-time cell analysis (RTCA), androgen-sensitive LNCaP cells (Lymph Node Carcinoma of the Prostate) and androgen-independent PC-3. Both cell lines were highly resistant to high doses of radiotherapy.

RESULTS:

A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade.

CONCLUSIONS:

These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.

KEYWORDS:

Androgen blockade; Apoptosis; Enzalutamide; Prostate cancer; Radiotherapy

PMID: 30858765 PMCID: PMC6395847 [Available on 2020-03-01] DOI: 10.1016/j.rpor.2019.02.002

[savingdaddy]

Thank you for sharing this study! Keeping this study in my saves. Best wishes, Kimberly

[Hidden]

How to know if you have an enzalutamide-sensitive prostate cancer? Would Foundation one test from biopsy give you that answer?

[pjoshea13 in reply to Hidden]

I think one would have to try it to be sure. -Patrick