Oxygen-Enhanced MRI Is a Major Advance in Tumor Hypoxia Imaging

Dewhirst, Mark W.; Birer, Samuel R.

doi:10.1158/0008-5472.can-15-2818

Cited by 53 publications

(46 citation statements)

References 41 publications

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“…There is evidence that patient selection can be achieved. In three clinical trials better outcome was found in patients who exhibited evidence for tumor hypoxia, prior to initiation of hypoxia mitigation + radiotherapy compared with radiotherapy alone (45). Thus, modification of hypoxia should not be attempted unless its presence can be verified in each subject's tumor.…”

Section: B Evidence For Hypoxia and The Need To Measure It For Hypoxmentioning

confidence: 99%

GBM radiosensitizers: dead in the water…or just the beginning?

et al. 2017

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Abstract:The finding that most GBMs recur either near or within the primary site after radiotherapy has fueled great interest in the development of radiosensitizers to enhance local control. Unfortunately, decades of clinical trials testing a wide range of novel therapeutic approaches have failed to yield any clinically viable radiosensitizers (1). However, it is well-recognized that temozolomide chemotherapy is administered concurrently with radiotherapy specifically as a radiosensitizer. Furthermore, it can be argued that many of the previous radiosensitizing strategies, for GBM and many other tumor types were not backed by firm pre-clinical evidence supporting a synergistic or additive interaction (2). Another poorly understood variable is lack of blood-brain barrier penetration as potential limitation for treatment efficacy, as until recently most clinical trials did not assess the actual drug levels in GBM tumors. Finally, despite an understanding that DNA repair status was an important variable for radiotherapy treatment responses dating back to the 1970's, the actual DNA repair pathways and proteins were only fully elucidated in the last decade. Here, we present recent progress in the use of small molecule DNA damage response inhibitors as GBM radiosensitizers. In addition, we discuss the latest progress in targeting hypoxia and oxidative stress for GBM radiosensitization. Introduction. The finding that most GBMs recur either near or within the primary site after radiotherapy has fueled great interest in the development of radiosensitizers to enhance local control. Unfortunately, decades of clinical trials testing a wide range of novel therapeutic approaches have failed to yield any clinically viable radiosensitizers (1). However, it is well-recognized that temozolomide chemotherapy is administered concurrently with radiotherapy specifically as a radiosensitizer. Furthermore, it can be argued that many of the previous radiosensitizing strategies, for GBM and many other tumor types were not backed by firm pre-clinical evidence supporting a synergistic or additive interaction (2). Another poorly understood variable is lack of blood-brain barrier penetration as potential limitation for treatment efficacy, as until recently most clinical trials did not assess the actual drug levels in GBM tumors. Finally, despite an understanding that DNA repair status was an important variable for radiotherapy treatment responses dating back to the 1970's, the actual DNA repair pathways and proteins were only fully elucidated in the last decade. Here, we present recent progress in the use of small molecule DNA damage response inhibitors as GBM radiosensitizers. In addition, we discuss the latest progress in targeting hypoxia and oxidative stress for GBM radiosensitization. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation

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Section: B Evidence For Hypoxia and The Need To Measure It For Hypoxmentioning

confidence: 99%

GBM radiosensitizers: dead in the water…or just the beginning?

et al. 2017

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“…We do not expect that this approach is suitable for all patients; patient selection is essential and treatment should be adapted for every patient. Patients with non-hypoxic tumours have generally a better prognosis [34][35][36][37][38] and probably do not need an aggressive treatment as presented. Based on pretreatment hypoxia and FDG PET/CT scans it can be decided to boost hypoxic or FDG subvolumes, or a combination.…”

Section: Discussionmentioning

confidence: 92%

“…Interobserver variability, differences in tissue fixation techniques, and increased storage time of the samples could negatively influence reproducibility. For example, Chung et al [36] found that cetuximab shows activity in tumours that do not express EGFR and concluded that EGFR determined by immunohistochemistry might not reflect the tumour biology.…”

Section: Discussionmentioning

confidence: 99%

“…By labelling the mAb with positron-emitting radionuclides, a technique called immuno-PET [35], the expression of the antigens can be quantified and the efficiency of the mAb treatment can be assessed. The binding process of the mAb to the antigens is relatively slow, hence a long lasting positron emitting radionuclide is needed with a long half-life, for example Zirconium-89 ( 89 Zr) or Iodine-124 ( 124 I) [36].…”

Section: Selecting Pet Tracers To Visualize Different Biological Procmentioning

confidence: 99%

“…None of the mentioned clinical trials used the baseline hypoxia status to select patients. This is a general problem with hypoxia targeting studies; as patient stratification is rare, the full potential of hypoxia targeting strategies are not fully explored [36]. We aimed to analyse the effect of nitroglycerin on tumour hypoxia and tumour vasculature for each individual patient, to ultimately predict the benefit of nitroglycerin on a patient level.…”

Section: Imaging Of Tumour Hypoxia Vasculature and Metabolismmentioning

confidence: 99%

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Visualization and quantification of tumour biology for personalized radiotherapy

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Smart Tumor Microenvironment‐Responsive Nanotheranostic Agent for Effective Cancer Therapy

Guo

Sun

et al. 2020

Adv Funct Materials

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The tumor microenvironment (TME), which includes acidic and hypoxic conditions, severely impedes the therapeutic efficacy of antitumor agents. Herein, MnO 2 -loaded, bovine serum albumin, and PEG co-modified mesoporous CaSiO 3 nanoparticles (CaM-PB NPs) are developed as a nanoplatform with sequential theranostic functions for the engineering of TME. The MnO 2 NPs generate O 2 in situ by reacting with endogenous H 2 O 2 , relieving the hypoxic state of the TME that further modulates the cancer cell cycle status to S phase, which improves the potency of co-loaded S phase-sensitive chemotherapeutic drugs. After the hypoxia relief, CaM-PB can sustainably release drugs due to the enlarged pores of mesoporous CaSiO 3 in the acidic TME, preventing the drug pre-leakage into the blood circulation and insufficient drug accumulation at tumor sites. Moreover, the Mn 2+ released from the MnO 2 NPs at tumor sites can potentially serve as a diagnostic agent, enabling the identification of tumor regions by T 1 -weighted magnetic resonance imaging during therapy. In vivo pharmacodynamics results demonstrate that these synergetic effects caused by CaM-PB NPs significantly contribute to the inhibition of tumor progression. Therefore, the CaM-PB NPs with sequential theranostic functions are a promising system for effective cancer therapy. Keywordshypoxia relief, mesoporous calcium silicate, sequential functions, sustained drug release, synergetic effects

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Oxygen-Enhanced MRI Is a Major Advance in Tumor Hypoxia Imaging

Cited by 53 publications

References 41 publications

GBM radiosensitizers: dead in the water…or just the beginning?

GBM radiosensitizers: dead in the water…or just the beginning?

Visualization and quantification of tumour biology for personalized radiotherapy

Smart Tumor Microenvironment‐Responsive Nanotheranostic Agent for Effective Cancer Therapy

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