• Journal of Yeungnam Medical Science
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• 제38권4호
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• pp.308-317
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• 2021

Cancer is the leading cause of death and is on the rise worldwide. Until 2010, the development of targeted treatment was mainly focused on the growth mechanisms of cancer. Since then, drugs with mechanisms related to tumor immunity, especially immune checkpoint inhibitors, have proven effective, and most pharmaceutical companies are striving to develop related drugs. Programmed cell death-1 and programmed cell death ligand-1 inhibitors have shown great success in various cancer types. They showed durable and sustainable responses and were approved by the U.S. Food and Drug Administration. However, the response to inhibitors showed low percentages of cancer patients; 15% to 20%. Therefore, combination strategies with immunotherapy and conventional treatments were used to overcome the low response rate. Studies on combination therapy have typically reported improvements in the response rate and efficacy in several cancers, including non-small cell lung cancer, small cell lung cancer, breast cancer, and urogenital cancers. The combination of chemotherapy or targeted agents with immunotherapy is one of the leading pathways for cancer treatment.

• Genomics & Informatics
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• 제18권4호
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• pp.35.1-35.7
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• 2020

Identifying the patterns of gene expression in breast cancers is essential to understanding their pathophysiology and developing anticancer drugs. Breast cancer is a heterogeneous disease with different subtypes determined by distinct biological features. Luminal breast cancer is characterized by a relatively high expression of estrogen receptor (ER) and progesterone receptor (PR) genes, which are expressed in breast luminal cells. In ~25% of invasive breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed; these cancers are categorized as the HER2 type. Triple-negative breast cancer (TNBC), in which the cancer cells do not express ER/PR or HER2, shows highly aggressive clinical outcomes. TNBC can be further classified into specific subtypes according to genomic mutations and cancer immunogenicity. Herein, we discuss the brief history of TNBC classification and its implications for promising treatments.

• Journal of Digestive Cancer Research
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• 제10권2호
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• pp.74-81
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• 2022

Colorectal peritoneal metastasis has been an incurable disease for centuries. However, since the new millennium, recent advancements in therapies are achieved with modern chemotherapeutic agents, target agents, and immune checkpoint blockade introduction. Modern chemotherapies, from a nearly nonexistent median survival if untreated, have raised the duration to 16 months with target agents. Experts have once again surpassed its limit by introducing intraperitoneal chemotherapy and cytoreductive surgery (CRS). Numerous clinical trials regarding CRS and hyperthermic intraperitoneal chemotherapy have now opened new doors in peritoneal carcinomatosis treatment, even securing complete remission. In addition, up-to-date modalities, such as pressurized intraperitoneal aerosol chemotherapy and immunotherapies, showed promising results at an early stage.

• 한국임상약학회지
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• 제28권2호
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• pp.88-94
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• 2018

Background: We strived to evaluate the status of nivolumab use and associated factors on the clinical efficacy of the drug. Methods: The study was retrospectively conducted in patients who had been administered nivolumab at least once at the cancer center of Seoul National University Hospital from June 2015 to April 2017. Data were collected from electronic medical records. A medication-use evaluation was performed based on the American Society of Health-System Pharmacists mediation-use guidelines. Results: Sixty-six of the 74 patients (89.2%) showed indications approved for nivolumab use by the Korean Ministry of Food and Drug Safety (MFDS; n=55) or the US Food and Drug Administration (FDA; n=11). Approximately 73.0% of the patients were administered the approved dose of 3 mg/kg but 25.7% were administered an unapproved fixed dose of 100 mg. The overall response rate was 21.7%, and the response rate of non-small cell lung cancer patients, who accounted for the largest number of indications, was 18.8%. Adverse reactions were found in 90.1% of the patients and were mostly mild (86%). The expression of programmed death-ligand 1 (PD-L1) was analyzed as a factor affecting treatment response (p=0.028, odds ratio [OR]=11.331). Conclusion: PD-L1 expression was found to affect treatment response. However, caution is required while using an unapproved dosage and in the absence of monitoring for effectiveness and safety. Therefore, an effective protocol or instruction manual for the proper use of nivolumab should be considered.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제41권
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• pp.56.1-56.6
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• 2019

Background: Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. Methods: A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. Results: The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. Conclusion: The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

• BMB Reports
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• 제51권11호
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• pp.572-577
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• 2018

Recent studies showed that the PD-1/PD-L1 checkpoint blockade is a dramatic therapy for melanoma by enhancing antitumor immune activity. Currently, major strategies for the PD-1/PD-L1 blockade have mainly focused on the use of antibodies and compounds. Seeking an alternative approach, others employ endogenous proteins as blocking agents. The extracellular domain of PD-1 (ePD1) includes the binding site with PD-L1. Accordingly, we constructed a PD-1-based recombinantly tailored fusion protein (dFv-ePD1) that consists of bivalent variable fragments (dFv) of an MMP-2/9-targeted antibody and ePD1. The melanoma-binding intensity and antitumor activity were also investigated. We found the intense and selective binding capability of the protein dFv-ePD1 to human melanoma specimens was confirmed by a tissue microarray. In addition, dFv-ePD1 significantly suppressed the migration and invasion of mouse melanoma B16-F1 cells, and displayed cytotoxicity to cancer cells in vitro. Notably, dFv-ePD1 significantly inhibited the growth of mouse melanoma B16-F1 tumor cells in mice and in vivo fluorescence imaging showed that dFv-ePD was gradually accumulated into the B16-F1 tumor. Also the B16-F1 tumor fluorescence intensity at the tumor site was stronger than that of dFv. This study indicates that the recombinant protein dFv-ePD1 has an intensive melanoma-binding capability and exerts potent therapeutic efficacy against melanoma. The novel format of the PD-L1-blocked agent may play an active role in antitumor immunotherapy.