The aim of the study was to collect and analyze published data from clinical trials on the efficacy of photodynamic therapy (PDT) using 5-ALA-based drugs and its esters in patients with basal cell carcinoma (BCC). The review was conducted using the PubMed and ClinicalTrials.gov databases for the period from 1995 to 2025. Large prospective and retrospective studies with more than 20 patients were included in the analysis. The efficacy of PDT was examined and compared with traditional treatment methods. The analysis demonstrated significant efficacy of PDT in the treatment of BCC. The complete regression rate ranged from 84% to 99% after 3 months of therapy, from 62% to 96% after 12 months, and from 70% to 91% after 5 years. A significantly better cosmetic outcome was recorded compared with surgical methods. Studies have confirmed that PDT has a high safety profile, with severe side effects rare. The most common adverse effects include mild skin irritation, redness, and mild discomfort, which resolve on their own.
Features of the expression of membrane importers of 5-ALA, as well as transporters involved in the removal of photoactive precursors of protoporphyrin IX (PPIX) (uro-, copro- and protoporphyrinogens), may cause differences in the effectiveness of photodynamic therapy of malignant neoplasms using 5-aminolevulinic acid (5-ALA). Increased expression of ALA transporters is associated with an increase in the intensity of PPIX synthesis. When the expression of PPIX exporters increases, there is a decrease in PPIX concentration. The review describes the main transporters of 5-ALA, uro-, copro- and protoporphyrinogens, provides data on their expression in various tissues, and discusses the possibility of predicting the effectiveness of photodynamic therapy considering the expression of the corresponding transport proteins in malignant tissues.
Bowen’s disease is a form of non-invasive (in situ) squamous cell skin cancer localized in the non-genital area. Russian and European clinical guidelines include photodynamic therapy (PDT) in the standard of care for patients with Bowen’s disease. In the present review, the efficacy and safety profile of different PDT regimens for Bowen’s disease are analyzed according to the available literature data. PDT can be used to treat large Bowen’s disease lesions localized in areas of the body characterized by severe healing and in cases where surgery is not feasible. Analysis of the results of studies shows that PDT is superior in efficacy and cosmetic results to traditional local treatments such as 5-fluorouracil or cryotherapy. In all analyzed studies in patients with Bowen’s disease, PDT achieved a significant clinical effect. Complete regression of pathologic foci was achieved in 67-100% of patients. In studies evaluating the recurrence rate of Bowen’s disease after PDT, this value ranged from 2-28% with the range of 6-18% in most of the studies. Most often, 5-aminolevulinic acid and its methyl ester are used for PDT in Bowen’s disease. According to some researchers, aminolevulinic acid allows to achieve a more long-term positive clinical effect with a lower incidence of painful reactions during treatment
Photodynamic therapy has traditionally been used and approved in many countries for the treatment of intraepithelial forms of cutaneous squamous cell carcinoma and precancer – actinic keratosis and Bowen’s disease. However, recently a number of studies have been conducted that suggest a possible expansion of the boundaries of photodynamic therapy for cutaneous squamous cell carcinoma. Several authors have suggested a therapeutic effect of photodynamic therapy for superficial, microinvasive and well-differentiated cutaneous squamous cell carcinoma. We reviewed publications on the website https://pubmed.ncbi.nlm.nih.gov devoted to this problem. Analysis of the research results shows that photodynamic therapy can achieve high efficiency and good cosmetic results in patients with microinvasive cutaneous squamous cell carcinoma, and in some cases even with an invasive form, and can be considered as an alternative to surgical treatment in patients with contraindications to surgery.
Extramammary Paget's disease is a rare neoplasm of apocrine gland-bearing areas of the skin. One of the most common localizations of such a tumor is the perianal area. Surgery is the most frequently reported therapy. However, it is an invasive procedure and complicated by a high recurrence rate. An alternative to surgical treatment may be non-invasive photodynamic therapy. We describe in this article the case of a 69-year-old patient with extramammary Paget's disease (a large tumor in the perianal area 22 × 18 cm) successfully treated with chlorin e6 photodynamic therapy.
Acne is one of the most common skin conditions in the world. A number of studies have shown that photodynamic therapy (PDT) is safe and effective for both inflammatory and non-inflammatory acne and can significantly improve skin conditions in this disease. The effectiveness of PDT against acne is mainly due to a decrease in the amount of sebum produced by the sebaceous glands due to a decrease in their activity as a result of direct photodynamic damage to the sebaceous glands, eradication of Cutibacterium acnes, and a decrease in the level of hyperkeratosis. Compared with systemic drug therapy, PDT treatment of severe acne has the following advantages: fast results, high efficiency, high selectivity, no systemic adverse reactions and drug resistance, and low recurrence rate. Most often for PDT in patients with acne, drugs based on 5-aminolevulinic acid (5-ALA) and its methyl ester (ME-ALA) are used. At the moment, there are no unified recommendations on PDT regimens for the treatment of this skin pathology. Various studies demonstrate the high efficiency of PDT with a wide range of doses of 5-ALA (3-20%) and ME-ALA (4-16%), light doses (15-120 J/cm2 ), and exposure time (30-90 min). The general trend in studies by different authors is that gentle low-intensity PDT regimens for acne demonstrate the same high efficiency with a significant reduction in pain during irradiation and local skin reactions (erythrema, edema, and hyperpigmentation).
Fluorescent diagnostics is a promising method for diagnosing non-melanocytic skin tumors, which makes it possible to identify clinically undetectable skin cancer foci and clarify the margin of the tumor lesion. The main drugs for uorescent diagnostics are drugs based on 5-aminolevulinic acid and its methyl ester. Sensitivity indicators of uorescent diagnostics in basal cell, squamous cell carcinoma and extramammary Paget’s disease reach 79.0-100.0%, speci city – 55.6-100%. But the effectiveness of this method may be reduced due to hyperkeratinization, keratinization, and the presence of necrotic tissue on the surface of tumor foci. Comparative studies of the results of uorescent diagnostics and histological mapping during tumor removal using Mohs micrographic surgery showed approximately equal results in the determining of the tumor edges by these methods, which indicates that safe and technically easily performed uorescent diagnostics can serve as a good alternative to Mohs micrographic surgery, one of the most accurate, but rather labor-intensive and technically complex method for determining the margin of skin cancer foci.
Sphingolipids are a diverse family of complex lipids typically composed of a sphingoid base bound to a fatty acid via amide bond. The metabolism of sphingolipids has long remained out of focus of biochemical studies. Recently, it has been attracting an increasing interest of researchers because of different and often multidirectional effects demonstrated by sphingolipids with a similar chemical structure. Sphingosine, ceramides (N-acylsphingosines), and their phosphorylated derivatives (sphingosine-1-phosphate and ceramide-1-phosphates) act as signaling molecules. Ceramides induce apoptosis and regulate stability of cell membranes and cell response to stress. Ceramides and sphingoid bases slow down anabolic and accelerate catabolic reactions, thus suppressing cell proliferation. On the contrary, their phosphorylated derivatives (ceramide-1-phosphate and sphingosine-1-phosphate) stimulate cell proliferation. Involvement of sphingolipids in the regulation of apoptosis and cell proliferation makes them critically important in tumor progression. Sphingolipid metabolism enzymes and sphingolipid receptors can be potential targets for antitumor therapy. This review describes the main pathways of sphingolipid metabolism in human cells, with special emphasis on the properties of this metabolism in tumor cells.
Photodynamic therapy (PDT) in the treatment of psoriasis remains the subject of much debate. There is no consensus in the scientific community about effective and safe PDT regimens for psoriasis. Described in the published materials doses and concentrations of photosensitizers for psoriasis, as well as light doses, differ by dozens of times. The purpose of this review is to analyze the efficacy and safety profile of various PDT regimens for psoriasis. Some studies demonstrate 100% effectiveness of the method in certain modes (complete or partial clearance of psoriasis foci after PDT). In particular, such efficiency was obtained with the application of 20% 5-ALA (light dose 15 J/cm2) and 0.1% methylene blue (light dose 15 J/ cm2). The main factor limiting the use of PDT in psoriasis, and in some cases even being the reason for treatment interruption, is severe pain during the irradiation procedure. This requires careful development of PDT regimens in patients with psoriasis.
Extramammary Paget’s disease (EMPD) is a rare tumor that predominantly affects the skin containing apocrine glands. Due to insufficient data on the effectiveness of different methods, there is no single therapeutic approach to the treatment of patients with EMPD and their subsequent management. The use of surgical methods, laser therapy and local cytotoxic drugs has a number of limitations. The advantages of using photodynamic therapy (PDT) in EMPD are the absence of systemic toxicity, non-invasiveness, selectivity of action, the absence of carcinogenic potential, the possibility of conducting several courses of treatment, and good cosmetic results. In our review, we analyzed those published in 2000-2022 data on the results of PDT treatment of 114 patients with EMPD. As a result of treatment, complete regression of tumor foci was achieved in 40% of patients. Most authors note that PDT is more effective for small areas (up to 4 cm2).
The review highlights the current understanding of the epidemiology, etiology, pathogenesis, existing classifications of mycosis fungoides. Methods for diagnosis and treatment of the pathology are described, among which photodynamic therapy (PDT) plays an important role. The main advantages of PDT for mycosis fungoides include the absence of systemic toxicity, non-invasiveness, selectivity, absence of carcinogenic potential, the possibility of repeated courses of treatment, and good cosmetic results. This review collects and analyzes the results of clinical trials of PDT in patients with mycosis fungoides. The analysis showed high efficiency of PDT in patients with mycosis fungoides with isolated or limited spots and plaques. PDT can be considered as the therapy of choice in patients with facial lesions when a good cosmetic result is one of the main requirements, and radiation therapy, nitrogen mustard or carmustine can leave permanent and visible scars. Plaques located in the axillary or inguinal skin folds that are inaccessible to phototherapy can also be treated with PDT.
The method of photodynamic therapy for treatment of malignant neoplasms is based on the selective of accumulation of photosensitizers in the tumor tissue. Insufficient selectivity of photosensitizers in relation to pathologically altered tissues and generalized distribution throughout the body leads to the development of severe toxic effects, including skin phototoxicity. The mechanisms underlying selectivity of photosensitizers for tumor tissue include selective binding to blood proteins and lipoproteins (considering that the number of receptors for those is increased on tumor cell membranes), uptake by macrophages, better solubility at low pH (acidic pH is characteristic of tumor cells), and other mechanisms. At present, increase in the efficiency of photodynamic therapy is largely associated with the additional targeting of photosensitizers to tumor tissues. Targeted delivery strategies are based on the differences in metabolism and gene expression profiles between the tumor and healthy cells. There are differences in expression of receptors, proteases, or transmembrane transporters in these cells. In particular, accelerated metabolism in many types of tumors leads to overexpression of receptors for epidermal growth factor, folic acid, transferrin, and a number of other compounds. This review considers biochemical basis for the selective accumulation of various classes of photosensitizers in tumors (chlorins, phthalocyanines, 5-aminolevulinic acid derivatives, etc.) and discusses various strategies of targeted delivery with emphasis on conjugation of photosensitizers with the receptor ligands overexpressed in tumor cells.
The article presents a clinical observation. The patient, 72 years old, applied to the MNII them. P.A. Herzen with complaints about the presence of an ulcerated tumor of the left ear. After further examination, a diagnosis was made - basal cell carcinoma of the ear skin with spread to the skin of the parotid region T3N0M0. On July 9, 2021, the patient underwent a course of photodynamic therapy (PDT) using a photosensitizer based on chlorin e6 and a diode laser with a wavelength of 662 nm. After one course of PDT, complete regression of the tumor was recorded.
The results of a 13-year clinical observation of a patient after treatment for basal cell carcinoma of the skin of the right cheek Ist cT1N0M0 are presented. The history of the course of the disease is associated with the fact that the patient underwent radiation therapy in early childhood for hemangioma of the lower eyelid of the right eye and right cheek. In 2008, against the background of post-radiation changes in the area of the right cheek, basal cell carcinoma was diagnosed at the Moscow Oncological Research Institute. P.A. Herzen. At the Center for Laser and Photodynamic Diagnostics and Tumor Therapy, the patient underwent organ-preserving PDT treatment. A course of photodynamic therapy (PDT) with 5-aminolevulic acid was carried out. Subsequently, the patient was followed up until 2021 without relapse in the PDT area. In 2016, the patient was diagnosed with a relapse of the disease in the form of a new focus of basal cell carcinoma of the upper eyelid skin on the right Iast cT1N0M0. The patient underwent a course of PDT with a chlorin e6-based photosensitizer. Complete regression of the tumor was achieved, the period of relapse-free follow-up was 5 years.
In the present review the authors analyzed the effectiveness of treatment of intraepithelial neoplasia I-II-III of the cervix (CIN), vulva (VIN) and vagina (VaIN) using photodynamic therapy (PDT). PDT is a method based on exposure to light after preliminary introduction of a photosensitizer into the body with the formation of singlet oxygen, which has a cytotoxic effect. The results of research on the use of PDT with various photosensitizers in the complex of therapeutic measures in patients with CIN, VIN, VaIN are presented. These data on the effectiveness and safety of PDT, ease of use allow this medical technology to be attributed to one of the most promising areas in the treatment of pathological intraepithelial changes of the cervix, vulva and vagina. The presented information allows focusing the attention on the PDT method and informing doctors and researchers about the broad prospects for applying this treatment method in clinical practice.
The results of a 13-year clinical observation of a patient after treatment for basal cell carcinoma of the skin of the right cheek Ist cT1N0M0 are presented. The history of the course of the disease is associated with the fact that the patient underwent radiation therapy in early childhood for hemangioma of the lower eyelid of the right eye and right cheek. In 2008, against the background of post-radiation changes in the area of the right cheek, basal cell carcinoma was diagnosed at the Moscow Oncological Research Institute. P.A. Herzen. At the Center for Laser and Photodynamic Diagnostics and Tumor Therapy, the patient underwent organ-preserving PDT treatment. A course of photodynamic therapy (PDT) with 5-aminolevulic acid was carried out. Subsequently, the patient was followed up until 2021 without relapse in the PDT area. In 2016, the patient was diagnosed with a relapse of the disease in the form of a new focus of basal cell carcinoma of the upper eyelid skin on the right Iast cT1N0M0. The patient underwent a course of PDT with a chlorin e6-based photosensitizer. Complete regression of the tumor was achieved, the period of relapse-free follow-up was 5 years.
The review is dedicated to the analysis of the effectiveness of the treatment of erythroplasia of Queyrat (EQ) using photodynamic therapy (PDT). Particular attention is paid to the relationship between EQ and human papillomavirus (HPV) infection. The data of various researchers are presented, confirming the correlation between the development of the EQ and the HPV infection, however, it is noted that due to the small number of studies it is difficult to draw reliable conclusions on the presence and strength of this connection. The mechanisms of PDT involved in the implementation of both the antitumor effect in the treatment of EQ and the antiviral effect against HPV are considered. The data of 12 clinical studies and observations of the results of PDT of the EQ conducted in recent years are analyzed. An analysis of literature data showed that in the treatment of EQ, one of the two photosensitizers is usually used locally: 5-aminolevulinic acid or 5-aminolevulinic acid methyl ester. The treatment parameters in all the analyzed studies were similar: exposure to the ointment for 3–5 hours followed by irradiation with a light dose of 37–105 J/cm2. The number of PDT courses in different studies varied from 1 to 19. The effectiveness of treatment varied widely in different studies and clinical observations. Most studies have demonstrated high efficacy of PDT with complete regression in 36–83% (100% in one study) and a relapse-free follow-up period of up to 51 months. However, there were also individual clinical observations of patients in whom the treatment with the method of PDT was ineffective. It is possible that the described results were associated with improperly selected regimes of PDT or a large lesion area. Most authors especially note a very good cosmetic effect and a complete absence of scars after the treatment. Thus, PDT is an effective and promising method for the treatment of EQ that requires, however, a more thorough development of the application regimen and a deeper study of the antitumor and antiviral components of the mechanism of action.
Topical 5-aminolevulinic acid-mediated photodynamic therapy is an established approach for the treatment of basal cell carcinoma. This study with 5- aminolevulinic acid drug Levulon was conducted in patients with superficial skin basal cell carcinoma. The study included 82 patients with overall number of tumor foci of 119. Tumor sites were as follows: head and neck, trunk, extremities.A total of two photodynamic therapy sessions, four weeks apart were performed using a laser with a wavelength of 630 nm and energy density of 350 J/cm(2). A complete response was recorded in 77 patients (114 foci) with an excellent cosmetic result. According to the analysis of survival in the group of patients with a complete response, the overall RFS was as follows: 1-year rate - 92.1 %, 3-year - 88.3 %. Photodynamic therapy with topical Levulon in patients with superficial BCC of the skin was effective and safe.