Growth factors mediated cell signalling in prostate cancer progression: Implications in discovery of anti-prostate cancer agents

Joshi, Gaurav; Singh, Pankaj Kumar; Negi, Arvind S.; Rana, Anil; Singh, Sandeep; Kumar, Raj

doi:10.1016/j.cbi.2015.08.009

Cited by 49 publications

(41 citation statements)

References 126 publications

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“…When PCa is localized to the prostate and surrounding tissues, surgery or radiotherapy can be used effectively in most patients [4]. The standard therapy for advanced/metastatic disease has been androgen deprivation therapy (ADT).…”

Section: Current Treatments For Prostate Cancermentioning

confidence: 99%

“…However, this approach often results in resistance and has recently become a less common therapeutic option [5]. Bilateral orchiectomy is one classical strategy for androgen suppression; however, this method is associated with numerous side effects and risk factors [4] and results in castration-resistant prostate cancer (CRPC). This method is rarely used in developed countries.…”

Section: Current Treatments For Prostate Cancermentioning

confidence: 99%

“…Unfortunately, these options lose efficacy over time as cancer cells develop resistance to ADT and proliferate despite the absence of androgen, progressing into CRPC. Before 2010, the only treatment shown to inhibit disease progression and improve overall survival for patients with CRPC was the drug docetaxel; however, this compound could only lengthen the life span of CRPC patients for a few months [4, 6]. Since 2010, five new therapeutics have been approved in the United States which extend median survival by only 3–5 months [7].…”

Section: Current Treatments For Prostate Cancermentioning

confidence: 99%

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Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer

Kallifatidis

Hoy

Lokeshwar

2016

Seminars in Cancer Biology

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Prostate cancer (PCa), a hormonally-driven cancer, ranks first in incidence and second in cancer related mortality in men in most Western industrialized countries. Androgen and androgen receptor (AR) are the dominant modulators of PCa growth. Over the last two decades multiple advancements in screening, treatment, surveillance and palliative care of PCa have significantly increased quality of life and survival following diagnosis. However, over 20% of patients initially diagnosed with PCa still develop an aggressive and treatment-refractory disease. Prevention or treatment for hormone-refractory PCa using bioactive compounds from marine sponges, mushrooms, and edible plants either as single agents or as adjuvants to existing therapy, has not been clinically successful. Major advancements have been made in the identification, testing and modification of the existing molecular structures of natural products. Additionally, conjugation of these compounds to novel matrices has enhanced their bio-availability; a big step towards bringing natural products to clinical trials. Natural products derived from edible plants (nutraceuticals), and common folk-medicines might offer advantages over synthetic compounds due to their broader range of targets, as compared to mostly single target synthetic anticancer compounds; e.g. kinase inhibitors. The use of synthetic inhibitors or antibodies that target a single aberrant molecule in cancer cells might be in part responsible for emergence of treatment refractory cancers. Nutraceuticals that target AR signaling (epigallocatechin gallate [EGCG], curcumin, and 5α-reductase inhibitors), AR synthesis (ericifolin, capsaicin and others) or AR degradation (betulinic acid, di-indolyl diamine, sulphoraphane, silibinin and others) are prime candidates for use as adjuvant or mono-therapies. Nutraceuticals target multiple pathophysiological mechanisms involved during cancer development and progression and thus have potential to simultaneously inhibit both prostate cancer growth and metastatic progression (e.g., inhibition of angiogenesis, epithelial-mesenchymal transition (EMT) and proliferation). Given their multi-targeting properties along with relatively lower systemic toxicity, these compounds offer significant therapeutic advantages for prevention and treatment of PCa. This review emphasizes the potential application of some of the well-researched natural compounds that target AR for prevention and therapy of PCa.

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Section: Current Treatments For Prostate Cancermentioning

confidence: 99%

Section: Current Treatments For Prostate Cancermentioning

confidence: 99%

Section: Current Treatments For Prostate Cancermentioning

confidence: 99%

See 1 more Smart Citation

Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer

Kallifatidis

Hoy

Lokeshwar

2016

Seminars in Cancer Biology

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“…The advent of the omics era, and resultant integrative genomic analyses of metastatic samples, has further highlighted the extent and frequency of AR pathway alterations in CRPC that may contribute to inappropriate activation or reactivation of this pathway (Grasso et al 2012, Beltran et al 2013, Azad et al 2015, Robinson et al 2015, Lallous et al 2016. Although these alterations have been the subject of other recent excellent articles (for example Penning 2014, Joshi et al 2015, Wyatt & Gleave 2015, this review will specifically focus on ADT-resistance mechanisms driven by direct structural changes to the AR and altered interplay between the AR and its coregulators. Finally, we will summarize the recent progress into the development of novel therapeutic strategies to target these specific resistance mechanisms.…”

Section: Mechanisms Of Persistent Ar Signaling Activity In Crpcmentioning

confidence: 99%

Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence

Coutinho¹,

Day²,

Tilley³

et al. 2016

Endocrine-Related Cancer

148

122

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The androgen receptor (AR) signaling axis drives all stages of prostate cancer, including the lethal, drug-resistant form of the disease termed castration-resistant prostate cancer (CRPC), which arises after failure of androgen deprivation therapy (ADT). Persistent AR activity in spite of ADT and the second-generation AR-targeting agents enzalutamide and abiraterone is achieved in many cases by direct alterations to the AR signaling axis. Herein, we provide a detailed description of how such alterations contribute to the development and progression of CRPC. Aspects of this broad and ever-evolving field specifically addressed in this review include: the etiology and significance of increased AR expression; the frequency and role of gain-of-function mutations in the AR gene; the function of constitutively active, truncated forms of the AR termed AR variants and the clinical relevance of alterations to the activity and expression of AR coregulators. Additionally, we examine the novel therapeutic strategies to inhibit these classes of therapy resistance mechanisms, with an emphasis on emerging agents that act in a manner distinct from the current ligand-centric approaches. Throughout, we discuss how the central role of AR in prostate cancer and the constant evolution of the AR signaling axis during disease progression represent archetypes of two key concepts in oncology, oncogene addiction and therapy-mediated selection pressure.

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“…Little irregularity in the process by mutation, genetic changes in the intracellular signaling in the RTKs may lead to cancer, diabetes, inflammation, arteriosclerosis, and angiogenesis [6,7]. The conventional treatment of cancer includes various strategies as surgery, chemotherapy, and radiotherapy, but gene network involved in cancer limits their benefits [8]. All these strategies prove to be fruitful with some side effects [9].…”

Section: Introductionmentioning

confidence: 99%

Triterpenes in cancer: significance and their influence

Gill

Kumar

Navgeet³

2016

Mol Biol Rep

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Natural products are enriched with numerous compounds with a broad spectrum of therapeutics indication suggesting the role of functional moieties as a core pharmacophore. This review highlights the role of triterpene in targeting signaling pathways in cancer. Advancement in cellular, biochemical, experimental, and computational approaches provides new insights into various pathways in cancer. In signaling network, triterpenes primarily target membrane receptors which control and modulates expression level of the biological responses. Triterpenes are immunomodulatory targeting nuclear factor kappa B, toll-like receptors, signal transducer and activator of transcription 3, and PI3K/Akt/mTOR. Triterpenes isolated from plants and fungus mainly focus on the process of apoptosis while other signaling areas in the cancer are still shrouded. Some of the triterpenes have already passed the clinical trial, whereas many more have been proven to yield effective results. This review would help the researchers to study the role of triterpenes in cancer, thus, helping them to discover and design efficacious therapeutics agents.

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Growth factors mediated cell signalling in prostate cancer progression: Implications in discovery of anti-prostate cancer agents

Cited by 49 publications

References 126 publications

Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer

Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer

Androgen receptor signaling in castration-resistant prostate cancer: a lesson in persistence

Triterpenes in cancer: significance and their influence

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