Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer
Adam M Kase,1 John A Copland III,2 Winston Tan1 1Mayo Clinic Florida Division of Hematology Oncology, Jacksonville, FL 32224, USA; 2Mayo Clinic Florida Department of Cancer Biology, Jacksonville, FL 32224, USACorrespondence: Adam M Kase Tel +1 904-953-0315Fax +1 905-953-2315Email kase.adam@mayo.eduA...
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doaj-ba1e51a4da6641dca7ec0e62981511e72020-11-25T03:37:34ZengDove Medical PressOncoTargets and Therapy1178-69302020-10-01Volume 13104991051358177Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate CancerKase AMCopland III JATan WAdam M Kase,1 John A Copland III,2 Winston Tan1 1Mayo Clinic Florida Division of Hematology Oncology, Jacksonville, FL 32224, USA; 2Mayo Clinic Florida Department of Cancer Biology, Jacksonville, FL 32224, USACorrespondence: Adam M Kase Tel +1 904-953-0315Fax +1 905-953-2315Email kase.adam@mayo.eduAbstract: The majority of patients with castrate-resistant prostate cancer will have metastatic disease at the time of diagnosis. Investigative efforts on new therapeutics for this patient population have improved with the development of androgen signaling inhibitors, such as abiraterone and enzalutamide, and PARP inhibitors, such as rucaparib and olaparib, to accompany the previously FDA-approved docetaxel, cabazitaxel, sipuleucel-T, and Radium 223. However, new therapeutic strategies are necessary to prolong survival as progression after these agents is inevitable. CDK4/6 inhibitors have advanced the field of estrogen receptor positive breast cancer treatment and are being investigated in prostate cancer given the role of androgen receptor signaling effects on the cell cycle. Response to CDK4/6 inhibitors may be predicted by the tumors’ genomic profile and may provide insight into combinatory therapy with CDK4/6 inhibitors in order to delay resistance or provide synergistic effects. Here, we review the use of CDK4/6 inhibitors in prostate cancer and potential combinations based on known resistance mechanisms to CDK4/6 inhibitors, prostate cancer regulatory pathways, and prostate-cancer-specific genomic alterations.Keywords: metastatic castrate-resistant prostate cancer, CDK4/6 inhibitors, genomics, combination therapyhttps://www.dovepress.com/novel-therapeutic-strategies-for-cdk46-inhibitors-in-metastatic-castra-peer-reviewed-article-OTTmetastatic castrate resistant prostate cancer cdk4/6 inhibitors genomics combination therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kase AM Copland III JA Tan W |
spellingShingle |
Kase AM Copland III JA Tan W Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer OncoTargets and Therapy metastatic castrate resistant prostate cancer cdk4/6 inhibitors genomics combination therapy |
author_facet |
Kase AM Copland III JA Tan W |
author_sort |
Kase AM |
title |
Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer |
title_short |
Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer |
title_full |
Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer |
title_fullStr |
Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer |
title_full_unstemmed |
Novel Therapeutic Strategies for CDK4/6 Inhibitors in Metastatic Castrate-Resistant Prostate Cancer |
title_sort |
novel therapeutic strategies for cdk4/6 inhibitors in metastatic castrate-resistant prostate cancer |
publisher |
Dove Medical Press |
series |
OncoTargets and Therapy |
issn |
1178-6930 |
publishDate |
2020-10-01 |
description |
Adam M Kase,1 John A Copland III,2 Winston Tan1 1Mayo Clinic Florida Division of Hematology Oncology, Jacksonville, FL 32224, USA; 2Mayo Clinic Florida Department of Cancer Biology, Jacksonville, FL 32224, USACorrespondence: Adam M Kase Tel +1 904-953-0315Fax +1 905-953-2315Email kase.adam@mayo.eduAbstract: The majority of patients with castrate-resistant prostate cancer will have metastatic disease at the time of diagnosis. Investigative efforts on new therapeutics for this patient population have improved with the development of androgen signaling inhibitors, such as abiraterone and enzalutamide, and PARP inhibitors, such as rucaparib and olaparib, to accompany the previously FDA-approved docetaxel, cabazitaxel, sipuleucel-T, and Radium 223. However, new therapeutic strategies are necessary to prolong survival as progression after these agents is inevitable. CDK4/6 inhibitors have advanced the field of estrogen receptor positive breast cancer treatment and are being investigated in prostate cancer given the role of androgen receptor signaling effects on the cell cycle. Response to CDK4/6 inhibitors may be predicted by the tumors’ genomic profile and may provide insight into combinatory therapy with CDK4/6 inhibitors in order to delay resistance or provide synergistic effects. Here, we review the use of CDK4/6 inhibitors in prostate cancer and potential combinations based on known resistance mechanisms to CDK4/6 inhibitors, prostate cancer regulatory pathways, and prostate-cancer-specific genomic alterations.Keywords: metastatic castrate-resistant prostate cancer, CDK4/6 inhibitors, genomics, combination therapy |
topic |
metastatic castrate resistant prostate cancer cdk4/6 inhibitors genomics combination therapy |
url |
https://www.dovepress.com/novel-therapeutic-strategies-for-cdk46-inhibitors-in-metastatic-castra-peer-reviewed-article-OTT |
work_keys_str_mv |
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