Optimal treatment of intermediate‐risk prostate carcinoma with radiotherapy

Nichol, Alan; Warde, Padraig; Bristow, Robert G.

doi:10.1002/cncr.21257

Cited by 50 publications

(35 citation statements)

References 150 publications

(132 reference statements)

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“…14 Therefore, pre-clinical data support two general aspects relating to the resistance of hypoxic tumours during RT: increased local tumour cell radioresistance 1 and/or an increased capacity for systemic metastases. 2 Clinical studies that have attempted to directly measure the level of hypoxia in CaP have used pO 2 electrodes, hypoxia imaging [positron emission tomography (PET)] and immunohistochemistry (IHC) [17][18][19][20][21][22][23][24][25] (Table 1).…”

Section: Tumour Hypoxia Measurements Are Prognostic In Localized Prosmentioning

confidence: 95%

“…This problem is illustrated by the fact that despite the use of stringent clinical criteria to place patients into clinical prognostic groups, 30-50% of males can still fail precision RT or surgery owing to local resistance and/or systemic spread. [1][2][3] Despite the publication of Phase III dose-escalated EBRT clinical trials in CaP designed to counteract failure due to CaP radioresistance, none of these trials have shown benefit in decreasing PCSM. 8 The lack of an effect on survival with EBRT dose escalation can be explained by the fact that in a significant proportion of patients, treatment failure is due to the presence of occult systemic disease rather than local resistance, and that these patients need to be treated with intensification of systemic therapy not EBRT dose intensification, to decrease CaP mortality.…”

mentioning

confidence: 99%

“…8 The lack of an effect on survival with EBRT dose escalation can be explained by the fact that in a significant proportion of patients, treatment failure is due to the presence of occult systemic disease rather than local resistance, and that these patients need to be treated with intensification of systemic therapy not EBRT dose intensification, to decrease CaP mortality. 1,8 Personalized CaP medicine therefore requires genomic-or biology-based biomarkers, in addition to existing clinical biomarkers, to explain interpatient heterogeneity in outcomes. Furthermore, even if an increased probability of occult metastases can be predicted, even more biomarkers will be required to favour the use of one systemic agent vs another, let alone the scheduling of these agents relative to each other ( Figure 1).…”

mentioning

confidence: 99%

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An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy

Bristow

Berlin²,

Pra

2014

BJR

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Prostate cancer (CaP) is the most commonly diagnosed malignancy in males in the Western world with one in six males diagnosed in their lifetime. Current clinical prognostication groupings use pathologic Gleason score, pre-treatment prostatic-specific antigen and Union for International Cancer Control-TNM staging to place patients with localized CaP into low-, intermediate-and high-risk categories. These categories represent an increasing risk of biochemical failure and CaP-specific mortality rates, they also reflect the need for increasing treatment intensity and justification for increased side effects. In this article, we point out that 30-50% of patients will still fail image-guided radiotherapy or surgery despite the judicious use of clinical risk categories owing to interpatient heterogeneity in treatment response. To improve treatment individualization, better predictors of prognosis and radiotherapy treatment response are needed to triage patients to bespoke and intensified CaP treatment protocols. These should include the use of pre-treatment genomic tests based on DNA or RNA indices and/or assays that reflect cancer metabolism, such as hypoxia assays, to define patient-specific CaP progression and aggression. More importantly, it is argued that these novel prognostic assays could be even more useful if combined together to drive forward precision cancer medicine for localized CaP.

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Section: Tumour Hypoxia Measurements Are Prognostic In Localized Prosmentioning

confidence: 95%

mentioning

confidence: 99%

mentioning

confidence: 99%

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An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy

Bristow

Berlin²,

Pra

2014

BJR

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“…Over the past three decades, the number of cases has increased five times [1]. Most patients have organ-confined or locally advanced tumours at the time of diagnosis [2].…”

Section: Introductionmentioning

confidence: 99%

“…Biochemical recurrence will occur in 15-50% of patients despite radical treatment; a part of patients will develop metastasis and die [2][3]. The rate of relapse depends on prognostic factors, such as the TNM stage, the degree of malignancy according to Gleason as well as the initial PSA (prostate-specific antigen) concentration.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia in prostate cancer

Danielska

Łuniewska-Bury²,

Kuncman³

et al. 2017

Nowotwory. Journal of Oncology

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Most human solid tumours contain areas which are less oxygenated than normal tissues. Hypoxia increases resistance to radiotherapy, surgery and chemotherapy, and directly alters the function of tumour cells, stimulating them to de-differentiate and to release angiogenic factors with a view to increasing the blood and oxygen supply. Tumour hypoxia promotes malignant progression and metastasis formation. HIF-1 is a heterodimeric transcription factor composed of regulated HIF-1a and constitutively expressed HIF-1b. Tumour-associated activation of HIF-1a seems to be primarily, however the result of adaptation to oxygen shortage. The presence of the HIF-1a subunit overexpression has been confirmed in many tumours, in prostate cancer, among others; the role it plays in its progression is yet to be explained. Numerous studies strongly emphasize the importance of evaluating the status of the HIF-1a transcription factor in predicting the clinical and biochemical recurrence of prostate cancer and its resistance to castration. NOWOTWORY J Oncol 2017; 67, 2: 132-136

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Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels

Liu

Yao

et al. 2015

BioFactors

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Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy.

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Optimal treatment of intermediate‐risk prostate carcinoma with radiotherapy

Cited by 50 publications

References 150 publications

An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy

An arranged marriage for precision medicine: hypoxia and genomic assays in localized prostate cancer radiotherapy

Hypoxia in prostate cancer

Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels

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