Personalizing Therapy for Metastatic Prostate Cancer: The Role of Solid and Liquid Tumor Biopsies

Author(s):  
Terence W. Friedlander ◽  
Colin C. Pritchard ◽  
Himisha Beltran

Although biopsies of metastatic prostate cancer are rarely undertaken in the clinical setting, there is increasing interest in developing personalized approaches to therapy by taking into account the genetic and phenotypic changes in an individual tumor. Indeed, analysis of metastatic prostate tumors can predict sensitivity to agents that inhibit DNA repair and resistance to novel hormonal agents, such as abiraterone and enzalutamide, and identify phenotypic changes, such as neuroendocrine differentiation, that have important clinical implications. Although obtaining metastatic tumor tissue is necessary for this genomic and molecular profiling, knowing when to biopsy, selecting the appropriate metastatic lesion, and interpreting the results are major challenges facing clinicians today. In this article, we discuss the rationale for obtaining metastatic tumor tissue, review the bioinformatic approach to analyzing these specimens, discuss the timing and approach to solid and liquid tumor biopsies, review the challenges associated with obtaining and acting on clinically relevant results, and discuss opportunities for the future.

2020 ◽  
Author(s):  
W Kisel ◽  
S Conrad ◽  
S Füssel ◽  
U Sommer ◽  
GB Baretton ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2795
Author(s):  
Sofia Papanikolaou ◽  
Aikaterini Vourda ◽  
Spyros Syggelos ◽  
Kostis Gyftopoulos

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.


Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1405 ◽  
Author(s):  
Patel ◽  
Chugh ◽  
Tripathi

Our understanding of neuroendocrine prostate cancer (NEPC) has assumed a new perspective in light of the recent advances in research. Although classical NEPC is rarely seen in the clinic, focal neuroendocrine trans-differentiation of prostate adenocarcinoma occurs in about 30% of advanced prostate cancer (PCa) cases, and represents a therapeutic challenge. Even though our knowledge of the mechanisms that mediate neuroendocrine differentiation (NED) is still evolving, the role of androgen deprivation therapy (ADT) as a key driver of this phenomenon is increasingly becoming evident. In this review, we discuss the molecular, cellular, and therapeutic mediators of NED, and emphasize the role of the tumor microenvironment (TME) in orchestrating the phenotype. Understanding the role of the TME in mediating NED could provide us with valuable insights into the plasticity associated with the phenotype, and reveal potential therapeutic targets against this aggressive form of PCa.


2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Yi Wang ◽  
Zhiqiang Qin ◽  
Yamin Wang ◽  
Chen Chen ◽  
Yichun Wang ◽  
...  

The recommended therapy by EAU guidelines for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without chemotherapy. The role of radical prostatectomy (RP) in the treatment of mPCa is still controversial. Hence, a meta-analysis was conducted by comprehensively searching the databases PubMed, EMBASE and Web of Science for the relevant studies published before September 1st, 2017. Our results successfully shed light on the relationship that RP for mPCa was associated with decreased cancer-specific mortality (CSM) (pooled HR = 0.41, 95%CI = 0.36–0.47) and enhanced overall survival (OS) (pooled HR = 0.49, 95%CI = 0.44–0.55). Subsequent stratified analysis demonstrated that no matter how RP compared with no local therapy (NLT) or radiation therapy (RT), it was linked to a lower CSM (pooled HR = 0.36, 95%CI = 0.30–0.43 and pooled HR = 0.56, 95%CI 0.43–0.73, respectively) and a higher OS (pooled HR = 0.49, 95%CI = 0.44–0.56 and pooled HR = 0.46, 95%CI 0.33–0.65, separately). When comparing different levels of Gleason score, M-stage or N-stage, our results indicated that high level of Gleason score, M-stage or N-stage was associated with increased CSM. In summary, the outcomes of the present meta-analysis demonstrated that RP for mPCa was correlated with decreased CSM and enhanced OS in eligible patients of involved studies. In addition, patients with less aggressive tumors and good general health seemed to benefit the most. Moreover, no matter compared with NLT or RT, RP showed significant superiority in OS or CSM. Upcoming prospective randomized controlled trials were warranted to provide more high-quality data.


2013 ◽  
Author(s):  
Shabnam Ziaee ◽  
Shirly Sieh ◽  
Chia-Yi Chu ◽  
Ruoxiang Wang ◽  
Dietmar Hutmacher ◽  
...  

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