Dataset Information

Profiles of Radioresistance Mechanisms in Prostate Cancer.

ABSTRACT: Radiation therapy (RT) is commonly used for the treatment of localized prostate cancer (PCa). However, cancer cells often develop resistance to radiation through unknown mechanisms and pose an intractable challenge. Radiation resistance is highly unpredictable, rendering the treatment less effective in many patients and frequently causing metastasis and cancer recurrence. Understanding the molecular events that cause radioresistance in PCa will enable us to develop adjuvant treatments for enhancing the efficacy of RT. Radioresistant PCa depends on the elevated DNA repair system and the intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and scavenge anti-cancer regimens, whereas the elevated heat shock protein 90 (HSP90) and the epithelial-mesenchymal transition (EMT) enable radioresistant PCa cells to metastasize after exposure to radiation. The up-regulation of the DNA repairing system, ROS, HSP90, and EMT effectors has been studied extensively, but not targeted by adjuvant therapy of radioresistant PCa. Here, we emphasize the effects of ionizing radiation and the mechanisms driving the emergence of radioresistant PCa. We also address the markers of radioresistance, the gene signatures for the predictive response to radiotherapy, and novel therapeutic platforms for targeting radioresistant PCa. This review provides significant insights into enhancing the current knowledge and the understanding toward optimization of these markers for the treatment of radioresistant PCa.

SUBMITTER: Chaiswing L

PROVIDER: S-EPMC6231577 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Profiles of Radioresistance Mechanisms in Prostate Cancer.

Chaiswing Luksana L Weiss Heidi L HL Jayswal Rani D RD Clair Daret K St DKS Kyprianou Natasha N

Critical reviews in oncogenesis 20180101 1-2

Radiation therapy (RT) is commonly used for the treatment of localized prostate cancer (PCa). However, cancer cells often develop resistance to radiation through unknown mechanisms and pose an intractable challenge. Radiation resistance is highly unpredictable, rendering the treatment less effective in many patients and frequently causing metastasis and cancer recurrence. Understanding the molecular events that cause radioresistance in PCa will enable us to develop adjuvant treatments for enhanc ...[more]

PMID: 29953367

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Project description:BackgroundThe problem of prostate cancer progression to androgen independence has been extensively studied. Several studies systematically analyzed gene expression profiles in the context of biological networks and pathways, uncovering novel aspects of prostate cancer. Despite significant research efforts, the mechanisms underlying tumor progression are poorly understood. We applied a novel approach to reconstruct system-wide molecular events following stimulation of LNCaP prostate cancer cells with synthetic androgen and to identify potential mechanisms of androgen-independent progression of prostate cancer.Methodology/principal findingsWe have performed concurrent measurements of gene expression and protein levels following the treatment using microarrays and iTRAQ proteomics. Sets of up-regulated genes and proteins were analyzed using our novel concept of "topological significance". This method combines high-throughput molecular data with the global network of protein interactions to identify nodes which occupy significant network positions with respect to differentially expressed genes or proteins. Our analysis identified the network of growth factor regulation of cell cycle as the main response module for androgen treatment in LNCap cells. We show that the majority of signaling nodes in this network occupy significant positions with respect to the observed gene expression and proteomic profiles elicited by androgen stimulus. Our results further indicate that growth factor signaling probably represents a "second phase" response, not directly dependent on the initial androgen stimulus.Conclusions/significanceWe conclude that in prostate cancer cells the proliferative signals are likely to be transmitted from multiple growth factor receptors by a multitude of signaling pathways converging on several key regulators of cell proliferation such as c-Myc, Cyclin D and CREB1. Moreover, these pathways are not isolated but constitute an interconnected network module containing many alternative routes from inputs to outputs. If the whole network is involved, a precisely formulated combination therapy may be required to fight the tumor growth effectively.

Dataset Information

Profiles of Radioresistance Mechanisms in Prostate Cancer.

Publications

Profiles of Radioresistance Mechanisms in Prostate Cancer.

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