# Photodynamic Therapy--An Up-to-Date Review
## 5 Photodynamic Therapy Applications
### Malignant Diseases  
Aiming to address the invasive nature of previous anticancer therapeutic strategies (e.g., radiotherapy, chemotherapy, surgery), PDT was developed as a promising alternative [8,15,16,106,107,108]. The main advantage of PDT is its selectivity to tumoral tissues, whereas non-malignant cell damage is minimized [29,109]. PDT can induce cancer cells' death through three inter-combined mechanisms: direct cellular damage by inducing ROS production, indirect damage by shutting down tumor blood vessels, and stimulation of the patient's immune system by increasing cancer cell-derived antigen presentation to T cells [109, 110, 111]. PDT was first used in human trials in 1976 for patients with bladder cancer. Afterward, promising responses were obtained from early-stage patients suffering from lung, esophageal and gastric carcinomas. The next studies included PDT in treating other tumors and cancer types, such as brain tumors, intraocular cancer, breast cancer, head and neck tumors, pancreatic cancer, gynecological tumors [12]. PDT can be employed in the treatment of skin cancers, both melanoma and non-melanoma, the latter being categorized into two subgroups, namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) [11,46,85,112]. Melanoma originates from the cells responsible for pigment production (melanocytes) and is the most aggressive of all forms, being likely to grow and spread if left untreated. Therefore, it is vital to diagnose this disease early and start treatment right away [113]. PDT is considered an alternative treatment for melanoma. However, some challenges still hinder its therapeutic efficacy, better tumor targeting, and near-infrared absorbing PSs being required [46]. On the other hand, non-melanoma skin cancers are most commonly found in the areas exposed to the sun [113]. BCC starts from the lower layer of the epidermis (made of basal cells) and tends to grow slowly, with only low metastatic potential [112]. In contrast, SCCs are more likely to extend towards deeper layers of the skin and invade other parts of the body, even though this is rather uncommon. Nonetheless, to avoid spreading to surrounding areas and create multicentric, synchronic, and metachronic lesions, these cancers should not be left untreated [112, 113, 114, 115]. In this respect, PDT has been proved to produce the most appropriate cosmetic and functional results [112]. However, patientstreated in this manner should be further monitored as there remains a risk of incomplete response and recurrence [114]. Breast cancer is the most common type of carcinoma in females, being the most prominent cause of cancer-related mortality in women worldwide [94; 106; 116; 117]. The first treatment option for breast cancer is the combination between chemotherapeutic agents, radiation therapy, and surgical intervention. Nonetheless, drugs do not yet penetrate tumor tissue at adequate levels, and systemic side effects are observed [94]. Overcoming these drawbacks, PDT is seen as a promising, safe, and minimally invasive procedure. Moreover, if part of a tumor of known and limited extent appears on an MRI scan, PDT treatment is much simpler to repeat than conventional therapies [118]. In terms of diagnosed cases and associated deaths, one of the top three cancers in the US is lung cancer [13]. Chemotherapy is the dominant treatment modality, yet cancer cells develop drug resistance and no longer respond to therapy after a while. Consequently, a new treatment strategy must be applied, either after chemotherapy becomes inefficient or as the main treatment modality [119]. In this respect, PDT has a long history of clinical success, being FDA-approved for the ablation of microinvasive endobronchial non-small cell lung cancer (NSCLC) not suitable for other treatments and of completely or partially obstructive endobronchial NSCLC [11; 13; 120]. In terms of incidence and mortality rate, the fourth most common malignancy among women globally is cervical cancer [121].