Photodynamic therapy (PDT) for malignant brain tumors – Where do we stand?

Quirk, Brendan J.; Brandal, Garth; Donlon, Steven; Vera, Juan Carlos; Mang, Thomas S.; Foy, Andrew B.; Lew, Sean M.; Girotti, Albert W.; Jogal, Sachin; LaViolette, Peter S.; Connelly, Jennifer; Whelan, Harry T.

doi:10.1016/j.pdpdt.2015.04.009

Cited by 187 publications

(158 citation statements)

References 75 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…The Brd4 inhibitor JQ1 suppressed iNOS expression, NO production, and cell hyper-aggressiveness much more powerfully than an inhibitor of iNOS enzymatic activity, suggesting that JQ1 or a related BET bromodomain inhibitor could greatly improve clinical PDT outcomes for glioblastoma and possibly other malignancies. A few examples of combining JQ1 with conventional radio-or chemotherapeutic approaches have been reported (54,77,78), but the present study represents the first time that JQ1 has been combined with PDT, which is recognized as one of the best treatment options for many solid tumors, including glioblastomas (67)(68)(69). Our findings from this in vitro study provide a strong incentive for more advanced work involving JQ1 in a mouse tumor PDT model, which will soon be underway.…”

Section: Discussionmentioning

confidence: 71%

Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1

Fahey

Stancill

Smith

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Endogenous nitric oxide (NO) generated by inducible NO synthase (iNOS) promotes glioblastoma cell proliferation and invasion, and also plays a key role in glioblastoma resistance to chemotherapy and radiotherapy. Non-ionizing photodynamic therapy (PDT) has anti-tumor advantages over conventional glioblastoma therapies. Our previous studies revealed that glioblastoma U87 cells upregulate iNOS after a photodynamic challenge and that resulting NO not only increased resistance to apoptosis, but rendered surviving cells more proliferative and invasive. These findings were largely based on the effects of inhibiting iNOS activity and scavenging NO. Demonstrating now that iNOS expression in photostressed U87 cells is mediated by NF-κB, we hypothesized that (i) recognition of acetylated lysine (acK) on NF-κB p65/Rel A by bromodomain and extra-terminal (BET) protein Brd4 is crucial, and (ii) by suppressing iNOS expression, a BET inhibitor (JQ1) would attenuate the negative effects of photostress. The following evidence was obtained: (i) Like iNOS, Brd4 protein and p65-acK levels increased several fold in photostressed cells; (ii) JQ1 at minimally toxic concentrations had no effect on Brd4 or p65-acK upregulation after PDT, but strongly suppressed iNOS, survivin, and Bcl-xL upregulation, along with the growth and invasion spurt of PDTsurviving cells; (iii) JQ1 inhibition of NO production in photostressed cells closely paralleled that of growth/invasion inhibition; (iv) At 1% the concentration of iNOS inhibitor 1400W, JQ1 reduced post-PDT cell aggressiveness to a far greater extent. This is the first evidence for BET inhibitor targeting of iNOS expression in cancer cells and how such targeting can markedly improve therapeutic efficacy.

show abstract

Section: Discussionmentioning

confidence: 71%

Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1

Fahey

Stancill

Smith

et al. 2018

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…PDT can be offered in an outpatient service, which is cost-effective and saves the patient a hospital stay [5,20,27]. A recent review focuses specifically on the use of PDT for the treatment of malignant brain tumours and provides a detailed and up-to-date summary of clinical investigations undertaken by numerous groups around the World [30]. It also highlights the difficulty in fully assessing the clinical impact of PDT because of the lack of control studies.…”

Section: Please Provide Corresponding Author(s) Photographmentioning

confidence: 99%

“…In terms of single photon activation the attenuation length is a key parameter describing the distance into the tissue or media where the applied light is reduced to approximately 37%. This parameter depends on numerous factors, including drug, ranging from 6.5 mm to ~ 1 mm for excised tumour and brain respectively using 600-700 nm light [30]. The ability to use further red-shifted wavelengths has potential benefits.…”

Section: Two-photon Pdt (2p-pdt)mentioning

confidence: 99%

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

Scherer

Bisby²,

Botchway³

et al. 2017

ACAMC

View full text Add to dashboard Cite

Photodynamic therapy (PDT) is an alternative cancer treatment to conventional surgery, radiotherapy and chemotherapy. It is based on activating a drug with light that triggers the generation of cytotoxic species that promote tumour cell killing. At present, PDT is mainly used in the treatment of wet age-related macular degeneration, for precancerous conditions of the skin (e.g. actinic keratosis) and in the palliative care of advanced cancers, for instance of the bladder or the oesophagus. Due to a lack of phase III clinical trials and limitations of light penetration to deeper lying tumours (in excess of 1 cm), PDT is still not used as a first line cancer treatment, which is surprising given the first clinical trials by Dougherty's group dating back to the 1970's. However research continues to demonstrate the potential benefits of PDT and the need to stimulate funding and uptake of clinical studies using next generation photosensitizers offering advanced targeted delivery, improved photodynamic dose combined with modern light delivery technologies. This review surveys the available PDT treatments and emerging novel developments in the field with a particular focus on two-photon techniques that are anticipated to improve the effectiveness of PDT in tissues at depth and on next generation drugs that work without the need of the presence of oxygen for photosensitization making them effective where hypoxia has taken hold.

show abstract

“…1 Currently, treatments often combine surgery, radiotherapy and chemotherapy, but a wide majority of GBM recurs locally, upwards of 80% of cases, leading to patient's death. 2 This indicates that a more aggressive local treatment is needed to improve the local control. However, resection can hardly be a complete and curative intervention because of the migration of tumor cells into the healthy brain parenchyma.…”

Section: Introductionmentioning

confidence: 99%

“…Ultrasmall aguIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma eloïse Thomas 1 ludovic colombeau 2 Mickaël gries 3,4 Thibaut Peterlini 3,4 clélia Mathieu 1 Noémie Thomas 3,4 cédric Boura 3,4 céline Frochot 2 régis Vanderesse 5 François lux 1 Muriel Barberi-heyob 3,4 Olivier Tillement 1…”

unclassified

Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma

Thomas¹,

Colombeau²,

Gries³

et al. 2017

IJN

View full text Add to dashboard Cite

Despite combined treatments, glioblastoma outcome remains poor with frequent local recurrences, indicating that a more efficient and local therapy is needed. In this way, vascular-targeted photodynamic therapy (VTP) could help tumor eradication by destroying its neovessels. In this study, we designed a polysiloxane-based nanoparticle (NP) combining a magnetic resonance imaging (MRI) contrast agent, a photosensitizer (PS) and a new ligand peptide motif (KDKPPR) targeting neuropilin-1 (NRP-1), a receptor overexpressed by angiogenic endothelial cells of the tumor vasculature. This structure achieves the detection of the tumor tissue and its proliferating part by MRI analysis, followed by its treatment by VTP. The photophysical properties of the PS and the peptide affinity for NRP-1 recombinant protein were preserved after the functionalization of NPs. Cellular uptake of NPs by human umbilical vein endothelial cells (HUVEC) was increased twice compared to NPs without the KDKPPR peptide moiety or conjugated with a scramble peptide. NPs induced no cytotoxicity without light exposure but conferred a photocytotoxic effect to cells after photodynamic therapy (PDT). The in vivo selectivity, evaluated using a skinfold chamber model in mice, confirms that the functionalized NPs with KDKPPR peptide moiety were localized in the tumor vessel wall.

show abstract

Photodynamic therapy (PDT) for malignant brain tumors – Where do we stand?

Abstract: Continued research in PDT will determine whether the advances shown will mitigate morbidity and mortality, but certainly the potential for this modality to revolutionize the treatment of brain tumors remains. The various uses for PDT in clinical practice should be pursued.

Cited by 187 publications

References 75 publications

Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1

Nitric oxide antagonism to glioblastoma photodynamic therapy and mitigation thereof by BET bromodomain inhibitor JQ1

New Approaches to Photodynamic Therapy from Types I, II and III to Type IV Using One or More Photons

Ultrasmall AGuIX theranostic nanoparticles for vascular-targeted interstitial photodynamic therapy of glioblastoma

Contact Info

Product

Resources

About