Photodynamic therapy in colorectal cancer treatment: The state of the art in clinical trials

doi:10.1016/j.pdpdt.2015.04.004

Photodiagnosis and Photodynamic Therapy

Volume 12, Issue 3, September 2015, Pages 545-553

https://doi.org/10.1016/j.pdpdt.2015.04.004 Get rights and content

Highlights

•
The general overview of photodynamic therapy application in colorectal cancer.
•
Promising trials results from I to II/III phase for the use of photodynamic therapy in the colorectal cancer.
•
Possibilities of PDT both in the less advanced tumors as well as in palliative therapy of advanced lesions.
•
PDT as a new safe and feasible treatment option for colorectal cancer.

Summary

Background

Photodynamic therapy (PDT) is used in many different oncologic fields. Also in gastroenterology, where have been a few attempts to treat both the premalignant lesion and advanced colorectal cancer. This review aims to give a general overview of the PDT application to colorectal cancer in the field of clinical trials to emphasize its curative, and insufficiently exploited potential.

Materials and methods

Literature on PDT for colorectal cancer with the following medical subject headings search terms: colorectal cancer, photodynamic therapy, clinical trials was reviewed. The articles were selected by their relevance to the topic.

Results

There are many positive and promising trial results from I to II/III phase for the use of PDT in colorectal cancer both in less advanced tumors as well as in the palliative therapy of advanced lesions.

Concluding remarks

PDT seems to be a safe and a feasible treatment option for colorectal cancer. Theoretical assumptions confirmed by many results of preclinical studies taking into consideration an increasing number of analyzed clinical trials, should lead to the development of optimized standards by using PDT in colorectal cancer treatment.

Introduction

The growing epidemic of cancer diseases is forcing scientists and clinicians from different specialties to seek new, safer and more effective therapeutic solutions. Every malignancy is a challenge for fighting by both patient and doctor, and colorectal cancer (CRC) is one of the best examples. On a global epidemiology, CRC is the third most common cancer and the fourth leading cause of deaths from oncological reasons [1], [2]. CRC is a cancer whose incidence increases every year in Europe by 2.5%. Despite the continuous development of science and medicine, a third of the patients in a moment of CRC diagnosis present metastases and in every other patient, despite radical treatment, cancer recurrence occurs [3]. Considering the above epidemiological data, CRC is still a challenge for modern medicine.

Significant prevalence, high invasiveness and metastatic potential with high probability of recurrence suggests the need for using radical methods with the most selective hitting to the cancer cells, which will increase the chances of their destruction, at the same time without causing damage to normal, surrounding tumor cells, minimizing the risk of perforation of the intestinal wall.

Such a method, which also has a high safety factor and in addition to local effects on focal lesion in the bowel also has a systemic one. It appears to be photodynamic therapy (PDT) which via secretion of chemokines and cytokines stimulates the immune system to antitumor activity [4], [5]. A slightly wider general application of PDT in oncology does not allow for its practical use in CRC treatment. It is a method which, despite very promising performances in research at both the experimental preclinical and clinical trials, is still not even taken into account in the guidelines. It could be rather an alternative or palliative method of CRC treatment, where many times due to the severity of the local tumor invasiveness or developing cancer cachexia, may be the only possible treatment offered to the patient.

PDT may be well applied in the treatment of precancerous lesions and even advanced tumors located in the large intestine via using endoscopic handle [6].

The purpose of this systematic review is to summarize the previous results, current evidence and the possibilities for PDT in patients with colorectal cancer.

Section snippets

Materials and methods

Several databases were searched from inception to January 2015 for studies that enrolled patients with colorectal cancer who received PDT (with various photosensitizers) for radical treatment or palliation of CRC.

We conducted a search of the following databases: Cochrane Central Register of Controlled Trials, Cochrane Databases of Systemic Reviews, EMBASE, MEDLINE, Scopus. Medical subject headings (MeSH) search terms were checked as follows: “photodynamic therapy”, “colorectal cancer”,

Clinical trials

Clinical trials have been the basis for the safe development of medicine since the Medical Research Council trial of using streptomycin for tuberculosis was published in 1948 [7]. In the absence of precise guidelines on the use of PDT in patients with colorectal cancer a large variety of PDT parameters appear in the analyzed: from the photosensitizer used, its concentration, the type and the dosage of light, or PDT application regimen to compatibility with traditional therapeutic methods.

Concluding remarks

Based on the above-mentioned studies, it appears that PDT is a relative, compared to surgery, chemo- and radiotherapy, safe method, given the high selectivity of accumulation of the photosensitizer in tumor cells, which guarantees the cytotoxic effect limited to pathological cells. High selectivity and reduce PDT action on a small, predictable surface and depth is the irrefutable attribute of this method, which guarantees, safety and low invasivness, which cannot be boasted by any of the

Conflicts of interest

The authors declare there are no conflicts of interest.

Acknowledgment

The study was supported by a grant from the Medical University of Silesia N^o KNW-1-058/N/4/0.

References (34)

J. Ferlay et al.
Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012
Eur J Cancer
(2013)
S.B. Brown et al.
The present and future role of photodynamic therapy in cancer treatment
Lancet Oncol
(2004)
T. Nakamura et al.
Photodynamic therapy with polypectomy for rectal cancer. Case reports
Gastrointest Endosc
(2003)
R.R. Allison et al.
Photodynamic therapy for anal cancer
Photodiagnosis Photodyn Ther
(2010)
H. Welbourn et al.
Can photodynamic therapy be the preferred treatment option for anal intraepithelial neoplasia? Initial results of a pilot study
Photodiagnosis Photodyn Ther
(2014)
Globocan
Estimated cancer incidence, mortality and prevalence worldwide in 2012. Information and online prediction
(2012)
R. Siegel et al.
Colorectal cancer statistics, 2014
CA: Cancer J Clin
(2014)
P.C. Kousius et al.
Photodynamic therapy enhancement of antitumor immunity is regulated by neutrophils
Cancer Res
(2007)
H. Barr et al.
Photodynamic therapy for colorectal cancer: a quantitative pilot study
Br J Surg
(1990)
Medical Research Council
Streptomycin treatment of pulmonary tuberculosis: a Medical Research Council investigation
BMJ
(1948)

H. Kashiwagi et al.

Gastroduodenal lesions in familial adenomatous polyposis

Surg Today

(2000)

L. Herrera-Ornelas et al.

Photodynamic therapy in patients with colorectal cancer

Cancer

(1986)

T. Patrice et al.

Endoscopic photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients

Digest Dis Sci

(1990)

N. Krasner

Laser therapy in the management of benign and malignant tumours in the colon and rectum

Int J Colorect Dis

(1989)

C.S. Loh et al.

Photodynamic therapy for villous adenomas of the colon and rectum

Endoscopy

(1994)

C.S. Loh et al.

Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy

Br J Cancer

(1993)

K.A. Hamdan et al.

Treatment of grade III anal intraepithelial neoplasia with photodynamic therapy. Report of a case

Dis Colon Rectum

(2003)

Cited by (84)

Exceptional anticancer photodynamic properties of [1,4-Bis(3,6,9,12-Tetraoxatridec-1-yloxy)phthalocyaninato]zinc(II)
2024, Journal of Photochemistry and Photobiology B: Biology
Phthalocyanines have been described as effective photosensitizers for photodynamic therapy and are therefore, being studied for their biomedical applications. The metalation of photosensitizers can improve their photodynamic therapy potential. Here, we focus on the biological properties of [1,4-Bis(3,6,9,12-Tetraoxatridec-1-yloxy)phthalocyaninato]zinc(II) (ZnPc(αEG₄)₂) and demonstrate its exceptional anticancer activity upon light stimulation to kill preferentially cancer cells with a start of efficiency at 10 pM. Indeed, in this work we highlighted the high selectivity of ZnPc(αEG₄)₂ for cancer cells compared with healthy ones and we establish its mechanism of action, enabling us to conclude that ZnPc(αEG₄)₂ could be a powerful tool for cancer therapy.
Whole-course care in photodynamic therapy of colorectal cancer: A short communication
2023, Photodiagnosis and Photodynamic Therapy
Photodynamic therapy is now widely used in different oncologic fields. It is feasible for the treatment of early, non-surgical and non-obstructive cancers. Also, in gastroenterology, where it was a few attempts to treat both the premalignant lesion and advanced colorectal cancer. Photodynamic therapy provides a new treatment option for advanced colon cancer patients with severe obstruction and elderly patients whose cardiopulmonary function cannot tolerate surgery, and effective nursing support throughout the treatment is the key to ensure successful treatment. This study reported the effect of whole-course care for colorectal cancer patients undergoing photodynamic therapy in the Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China.
Regulating <sup>1</sup>O<inf>2</inf> generation from heavy-atom-free triplet photosensitizers based on thiophene-fused BODIPY
2023, Dyes and Pigments
Triplet photosensitizers (PSs) used in photodynamic therapy (PDT) exhibit a strong relationship between the intersystem crossing (ISC) and generation of singlet oxygen (¹O₂). However, the effective design of PS molecules, particularly, heavy-atom-free PS, remains challenging due to limited understanding of the correlation between ISC rate (k_ISC) and the quantum yield of ¹O₂ generation (Φ_Δ). We present a case study for designing heavy-atom-free PSs (R–SB) via a combination of experimental and theoretical investigations. Electron-donating groups were introduced to the thiophene-fused BODIPY core. The measured Φ_Δ increased as the calculated k_ISC increased. The remarkable agreement between the experimental and theoretical findings improved our understanding of the ISC process in R–SB structures and established a framework for the potential future molecular design of heavy-atom-free PSs based on the BODIPY core. Among the various R–SB structures synthesized, carbazolyl benzene (Cbz) -SB exhibited fluorescence emission and was the most effective for ¹O₂ generation. Cbz-SB was further utilized for mitochondria-targeted fluorescence bioimaging and the PDT of HeLa cells, demonstrating its potential applicability in the respective areas.
Dendrobium officinale polysaccharide-based carrier to enhance photodynamic immunotherapy
2023, Carbohydrate Polymers
Photodynamic therapy (PDT) eradicates tumors via the generation of toxic reactive oxygen species (ROS) by activation of a photosensitizer (PS) with appropriate light. Local PDT toward tumors can trigger the immune response to inhibit distant tumors, but the immune response is usually insufficient. Herein, we used a biocompatible herb polysaccharide with immunomodulatory activity as the carrier of PS to enhance the immune inhibition of tumors after PDT. The Dendrobium officinale polysaccharide (DOP) is modified with hydrophobic cholesterol to serve as an amphiphilic carrier. The DOP itself can promote dendritic cell (DC) maturation. Meanwhile, TPA-3BCP are designed to be cationic aggregation-induced emission PS. The structure of one electron-donor linking to three electron-acceptors endows TPA-3BCP with high efficiency to produce ROS upon light irradiation. And the nanoparticles are designed with positively charged surfaces to capture antigens released after PDT, which can protect the antigens from degradation and improve the antigen-uptake efficiency by DCs. The combination of DOP-induced DC maturation and antigen capture-increased antigen-uptake efficiency by DCs significantly improves the immune response after DOP-based carrier-mediated PDT. Since DOP is extracted from the medicinal and edible Dendrobium officinale, the DOP-based carrier we designed is promising to be developed for enhanced photodynamic immunotherapy in clinic.
Stimulatory effects of wavelength-dependent photobiomodulation on proliferation and angiogenesis of colorectal cancer
2022, Journal of Photochemistry and Photobiology B: Biology
In recent decades, the laser treatment of cancer has been introduced as a promising treatment option. Because of the maldistribution of optical energy and an ambiguous boundary between the normal and tumor tissues, laser irradiation can stimulate residual cancer cells, leading to a cancer regrowth. As photobiomodulation (PBM) is involved in an extensive range of cellular responses, profound comprehension of photo-stimulated mechanisms against the cancer cells is required to establish a safety margin for PBM. Therefore, we aimed to identify the stimulant effects of PBM at various wavelengths against the tumor cells to establish a safety margin for the laser treatment. CT26 murine colon cancer cells were exposed to either 405 (BL), 635 (VIS), or 808 (NIR) nm laser lights at the fluences of 0, 10, 30, and 50 J/cm². In addition, CT26 tumor-bearing mice were irradiated with BL, VIS, or NIR at a fluence of 30 J/cm². Both the proliferation and angiogenesis potential of the CT26 cells and tumors were evaluated using the MTT assay, western blot, and immunohistochemistry (IHC) staining analyses. Although cell viability was not statistically significant, BL significantly induced p-ERK upregulation in the CT26 cells, indicating that PBM with BL can stimulate proliferation. In vivo tests showed that the NIR group exhibited the maximum relative tumor volume, and BL yielded a slight increase compared to the control. In the IHC staining and western blot analyses, both BL and NIR increased the expression of EGFR, VEGF, MMP-9, and HIF-1α, which are related to the proliferation and angiogenesis-related factors. Further investigations will be pursued to clarify the molecular pathways that depend on the cancer cell types and laser wavelengths for the establishment of safety guidelines in clinical environments.
Intestinal stents: Structure, functionalization and advanced engineering innovation
2022, Biomaterials Advances
Intestinal stents are a palliative treatment option that solves many shortcomings of traditional surgeries for cancer-induced intestinal obstructions. The present review provides an overview of the incidence, clinical manifestations and limitations in the treatment of intestinal cancers. The paper also discusses material property requirements, indications, complications and the future of stent-assisted therapy. The advantages and disadvantages of different materials and processing techniques for intestinal stents are reviewed along with new stent treatment combinations for colorectal cancer. Challenges that require further cooperative studies are also detailed. The future development of intestinal stents will depend on innovation in material designs as well as the utilization of multi-functional strategies and innovative engineering solutions.

View all citing articles on Scopus

View full text

ReviewPhotodynamic therapy in colorectal cancer treatment: The state of the art in clinical trials

Highlights

Summary

Background

Materials and methods

Results

Concluding remarks

Introduction

Section snippets

Materials and methods

Clinical trials

Concluding remarks

Conflicts of interest

Acknowledgment

Eur J Cancer

Lancet Oncol

Gastrointest Endosc

Photodiagnosis Photodyn Ther

Photodiagnosis Photodyn Ther

Estimated cancer incidence, mortality and prevalence worldwide in 2012. Information and online prediction

Colorectal cancer statistics, 2014

CA: Cancer J Clin

Photodynamic therapy enhancement of antitumor immunity is regulated by neutrophils

Cancer Res

Photodynamic therapy for colorectal cancer: a quantitative pilot study

Br J Surg

Streptomycin treatment of pulmonary tuberculosis: a Medical Research Council investigation

BMJ

Gastroduodenal lesions in familial adenomatous polyposis

Surg Today

Photodynamic therapy in patients with colorectal cancer

Cancer

Endoscopic photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients

Digest Dis Sci

Laser therapy in the management of benign and malignant tumours in the colon and rectum

Int J Colorect Dis

Photodynamic therapy for villous adenomas of the colon and rectum

Endoscopy

Oral versus intravenous administration of 5-aminolaevulinic acid for photodynamic therapy

Br J Cancer

Treatment of grade III anal intraepithelial neoplasia with photodynamic therapy. Report of a case

Dis Colon Rectum

Review
Photodynamic therapy in colorectal cancer treatment: The state of the art in clinical trials