Zoledronic acid for the treatment of prostate cancer

Finianos, Antoine; Aragon‐Ching, Jeanny B.

doi:10.1080/14656566.2019.1574754

Cited by 27 publications

(21 citation statements)

References 91 publications

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“…Bisphosphonates are a gold standard for the medical management of metastatic bone disease to inhibit bone resorption (Saad et al, 2006). Zol prevents bone complications as it inhibits osteoblastic and osteolytic metastases of prostate cancer and therefore improves life quality (Finianos and Aragon-Ching, 2019). We treated PCa cells with Zol and measured the mRNA expression of ALDH1A1 and ALDH1A3 .…”

Section: Resultsmentioning

confidence: 99%

The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

Gorodetska

Offermann

Pueschel

et al. 2021

Preprint

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Cancer stem cells (CSC) are characterized by high self-renewal capacity, tumor-initiating potential, and therapy resistance. Aldehyde dehydrogenase (ALDH)+ cell population serves as an indicator of prostate CSCs with increased therapy resistance, enhanced DNA double-strand break repair, and activated epithelial-mesenchymal transition (EMT) and migration. Numerous ALDH genes contribute to ALDH enzymatic activity; however, only some of them showed clinical relevance. We found that ALDH1A1 and ALDH1A3 genes functionally regulate CSC properties and radiation sensitivity of PCa. We revealed a negative correlation between ALDH1A1 and ALDH1A3 expression in publicly available prostate cancer (PCa) datasets and demonstrated that ALDH1A1 and ALDH1A3 have opposing predictive value for biochemical recurrence-free survival. Our data suggest an association of ALDH1A1 with the metastatic burden, elucidating the role of ALDH genes in the metastatic spread and homing to the bone, which can be, at least partially, attributed to regulating the transforming growth factor beta 1 (TGFB1) and matrix metalloproteinases (MMPs). ALDH genes play a diverse role in PCa development under AR and β-catenin-dependent regulation, with ALDH1A1 becoming dominant in later stages of tumor development when PCa cells gain androgen independence. Taken together, our results indicate that ALDH1A1 and ALDH1A3 modulate PCa radiosensitivity, regulate CSCs phenotype, and spread of PCa cells to the bone, therefore having clinical implication for identifying patients at high risk for progression to metastatic disease.

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Section: Resultsmentioning

confidence: 99%

The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

Gorodetska

Offermann

Pueschel

et al. 2021

Preprint

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“…Based on their strong inhibitory effect on osteoclasts, N-BPs are used to treat osteolytic bone metastases, which are frequent in advanced cancer, especially prostate and breast cancer. In PCa, ZOL has become an established first-line or adjunctive treatment in bone-targeted therapy for metastatic castrationresistant progression (223,232). Though ZOL delays skeletalrelated events (SREs), it reportedly has no effect on overall survival, other disease-oriented parameters, or radiographic progression improvement.…”

Section: Targeting Fpps In Clinical Cancer Therapymentioning

confidence: 99%

“…Though ZOL delays skeletalrelated events (SREs), it reportedly has no effect on overall survival, other disease-oriented parameters, or radiographic progression improvement. It remains an important adjunctive treatment strategy in the care of metastatic castrate-resistant PCa patients (223). Findings in clinical trials indicate that the beneficial effect of ZOL on bone metastasis from advanced prostate cancer might be related to long-term therapy, generally for more than 2 years (226).…”

Section: Targeting Fpps In Clinical Cancer Therapymentioning

confidence: 99%

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy

et al. 2020

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Recently, targeting metabolic reprogramming has emerged as a potential therapeutic approach for fighting cancer. Sterol regulatory element binding protein-2 (SREBP-2), a basic helix-loop-helix leucine zipper transcription factor, mainly regulates genes involved in cholesterol biosynthesis and homeostasis. SREBP-2 binds to the sterol regulatory elements (SREs) in the promoters of its target genes and activates the transcription of mevalonate pathway genes, such as HMG-CoA reductase (HMGCR), mevalonate kinase and other key enzymes. In this review, we first summarized the structure of SREBP-2 and its activation and regulation by multiple signaling pathways. We then found that SREBP-2 and its regulated enzymes, including HMGCR, FPPS, SQS, and DHCR4 from the mevalonate pathway, participate in the progression of various cancers, including prostate, breast, lung, and hepatocellular cancer, as potential targets. Importantly, preclinical and clinical research demonstrated that fatostatin, statins, and N-BPs targeting SREBP-2, HMGCR, and FPPS, respectively, alone or in combination with other drugs, have been used for the treatment of different cancers. This review summarizes new insights into the critical role of the SREBP-2-regulated mevalonate pathway for cancer and its potential for targeted cancer therapy.

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“…Actually, the development of castration resistance state is markedly triggered by orchestration of several critical factors including AR dependent and independent pathways, interactions between AR signaling and alternative survival pathways, neuroendocrine transdifferentiation, prostate cancer stem cell, autophagy, tumor hypoxia, microenvironment, immune-suppression and selective pressure provided by ADT [8,53,53,125]. Similarly, prostate cancer bone metastasis which adversely effects more than 90% of advanced prostate cancer patient is also an extremely pathologically complex phenomenon that is quite difficult to treat effectively with a single molecularly targeted agent like Denosumab or Zoledronic acid [126,127]. This mechanistic complexities mainly arises due to persistence of complex reciprocal interactions between prostate tumor cell and bone microenvironment at multiple levels like prostate tumor-bone stromal cell (osteoblast & osteoclast), prostate tumor-bone matrix and tumor-vasculature interactions [76,113,128].…”

Section: Future Strategic Directions Towards More Effective Therapeutic Targeting In Advanced Prostate Cancermentioning

confidence: 99%

A comprehensive mechanistic basis of prostate cancer advancement & its personalized implementation-bridging the gap: present state and future prospect

2021

JOMH

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Despite signiﬁcant achievements in prostate cancer mechanistic understanding and its targeted therapies, currently there exists several major challenges that mainly arises during the therapy of advanced prostate cancer. Present prostate cancer precision medicine strategy principally suffers from several practical concerns, particularly in point of therapeutic resistance, tumor heterogeneity, complex clinical & pathological behavior and an extensive genomic perturbation landscape. Prostate Cancer Systems-Medicine Initiative is a global trans-disciplinary movement taken from corre-sponding scientiﬁc domains to critically determine the nature of this major existing challenges and its corresponding most possible solutions by systematically accumulating the present existing knowledge. Basically, it explains the importance of broad spectrum cancer hallmark based integrative approaches for development of combination therapy associated strategic measures for metastatic castration resistant prostate cancer. The major ﬁndings of this initiative can be summarized by identiﬁcation of 136 therapeutic resistance mediators, 103 prostate cancer driver oncogenes and 8 progression pathways along with 5 terrain factors which centrally drives the basic events in prostate cancer pathogenesis, its further metastatic propagation and ultimate therapeutic resistance. In addition, it also attempts to summarize the critical features and basic challenging aspects of current therapeutic options.

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Zoledronic acid for the treatment of prostate cancer

Cited by 27 publications

References 91 publications

The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases

Targeting SREBP-2-Regulated Mevalonate Metabolism for Cancer Therapy

A comprehensive mechanistic basis of prostate cancer advancement & its personalized implementation-bridging the gap: present state and future prospect

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