tetraphenylporphine and Ovarian-Neoplasms

Ovarian cancer belongs to the group of gynecological cancers and indicates the high resistance to many drugs used in standard anticancer therapy. The treatment of ovarian cancer is a big challenge for the present medicine. In our report we tested the effectiveness of the combination anticancer therapy against ovarian cells: human ovarian carcinoma (A2780) and human ovarian fibroblasts (HOF). Two different types of drugs were used: doxorubicin (DOX) and a new-generation photosensitizer, nanoencapsulated meso-tetraphenylporphyrin (nano-TPP). The aim of the research was to compare the effect of the sequential combination therapy (chemotherapy with DOX and photodynamic therapy with nano-TPP) carried out in static and dynamic conditions. To achieve dynamic culture conditions, similar to in vivo environment, we designed a new microfluidic system in which the simultaneous, independent cultures of two cell lines (non-malignant and cancer cells) and their one-step analysis were possible. We observed that the sequential combination of photodynamic therapy (PDT) with chemotherapy allowed to obtain the synergistic effect of the treatment with using low doses of drugs. We also confirmed that the use of microfluidic conditions significantly increased the effectiveness of combination therapy and allowed for maintaining a high selectivity of the action of drugs on cancer cells. To the best of our knowledge, for the first time the microfluidic system was used to carry out sequential combination therapy against ovarian cancer.

Topics: Antibiotics, Antineoplastic; Cell Proliferation; Cell Survival; Cells, Cultured; Combined Modality Therapy; Dose-Response Relationship, Drug; Doxorubicin; Drug Screening Assays, Antitumor; Female; Humans; Microfluidic Analytical Techniques; Ovarian Neoplasms; Photosensitizing Agents; Porphyrins; Structure-Activity Relationship

Partly due to delays in its diagnosis, ovarian cancer's prognosis remains dire after primary therapy. Treatment consists in complete cytoreductive surgery and platinum-based chemotherapy. Recurrence rates are disappointingly high, as 60% of women with advanced epithelial ovarian cancer considered in remission will develop recurrent disease within five years. Special attention to undetected peritoneal metastasis and residual tumorous cells during surgery is necessary as they are the main predictors of recurrences. Targeted therapies aim to bring chemotherapy, radiotherapy and selective tumor photosensitizer (PS) agents to the targeted cell and its tumoral microenvironment. Folate receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells. Indeed, with good specificity and frequent overexpression in ovarian cancer, FRα is a recurrent topic in recent publications. The aim of this review is to present FRα and the reasons that make it an ideal targeting ligand for ovarian carcinoma therapy. Prophylactic photodynamic therapy (PPDT) using new generation FRα-coupled agents combined with complete cytoreductive surgery could allow for a significant decrease in recurrence rates. Preclinical trials are being run in order to allow for human clinical applications.

Topics: Drug Combinations; Female; Folate Receptor 1; Folic Acid; Humans; Molecular Targeted Therapy; Ovarian Neoplasms; Peritoneal Neoplasms; Photochemotherapy; Photosensitizing Agents; Porphyrins