Abstract
Ovarian cancer (OvCa) is the leading cause of gynecological cancer-related deaths in the United States, with five-year survival rates of 15–20% for stage III cancers and 5% for stage IV cancers. The standard of care for advanced OvCa involves surgical debulking of disseminated disease in the peritoneum followed by chemotherapy. Despite advances in treatment efficacy, the prognosis for advanced stage OvCa patients remains poor and the emergence of chemoresistant disease localized to the peritoneum is the primary cause of death. Therefore, a complementary modality that is agnostic to typical chemo- and radio-resistance mechanisms is urgently needed. Photodynamic therapy (PDT), a photochemistry-based process, is an ideal complement to standard treatments for residual disease. The confinement of the disease in the peritoneal cavity makes it amenable for regionally localized treatment with PDT. PDT involves photochemical generation of cytotoxic reactive molecular species (RMS) by non-toxic photosensitizers (PSs) following exposure to non-harmful visible light, leading to localized cell death. However, due to the complex topology of sensitive organs in the peritoneum, diffuse intra-abdominal PDT induces dose-limiting toxicities due to non-selective accumulation of PSs in both healthy and diseased tissue. In an effort to achieve selective damage to tumorous nodules, targeted PS formulations have shown promise to make PDT a feasible treatment modality in this setting. This targeted strategy involves chemical conjugation of PSs to antibodies, referred to as photoimmunoconjugates (PICs), to target OvCa specific molecular markers leading to enhanced therapeutic outcomes while reducing off-target toxicity. In light of promising results of pilot clinical studies and recent preclinical advances, this review provides the rationale and methodologies for PIC-based PDT, or photo-immunotherapy (PIT), in the context of OvCa management.
Highlights
Ovarian carcinoma (OvCa) is the leading cause of death from gynecological cancers and is the fifth most frequent cause of cancer-related deaths among women in the United States
A number of chemotherapeutic regimens exist for OvCa, and the reader is referred to excellent reviews on the current state of chemotherapy regimens [4,5,6,7]
Photodynamic therapy (PDT) is based on the observation that certain formulations of PSs accumulate preferentially in PDT is based on the observation that certain formulations of PSs accumulate preferentially in malignant tissues [27,28,29]
Summary
Ovarian carcinoma (OvCa) is the leading cause of death from gynecological cancers and is the fifth most frequent cause of cancer-related deaths among women in the United States. The high recurrence rate even among patients with negative second-look laparotomies is partly attributed to micrometastatic tumor nodules in the peritoneum that are invisible to the eye [25] Strategies to address these deadly pockets of disease utilizing mechanistically distinct combination therapies that exploit non-overlapping molecular targets represent a promising direction of research in PIT-based treatment of OvCa. PIT has demonstrated promise in overcoming the challenges associated with this deadly disease, and this review will give an overview of preclinical and clinical developments of this therapy and perspective of PIT’s potential role in treating OvCa. PDT; photosensitizer is administered systemically, followed byappropriate an appropriate. From Nath et al (2019) [26]
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