• Journal of Digestive Cancer Reports
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• v.8 no.1
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• pp.65-70
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• 2020

Although being one of the major causes of malignancy related death globally, hepatocellular carcinoma (HCC) has not received much attention in respect of novel drug development. Fortunately, several new drugs were found to be effective and tolerable in patients with advanced HCC from a number of phase 3 studies during the recent several years. Novel multi-targeted kinase inhibitors and immune checkpoint inhibitors were approved for clinical use, and combination strategies to maximize the potent of drugs demonstrated promising antitumor activity and safety with high response rate and improved safety profile. The increased number of available agents for HCC will contribute to change of treatment strategies and prognosis of patients with advanced HCC. Still, there is a many critical questions remain unanswered. Currently ongoing trials and future studies will provide better understanding of tumor biology and optimized criteria for patient selection and combination therapies.

• Tuberculosis and Respiratory Diseases
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• v.83 no.1
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• pp.14-19
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• 2020

Lung cancer remains the most common cause of cancer-related deaths worldwide. Although there are many possible treatments, including targeted therapies such as epidermal growth factor receptor tyrosine kinase inhibitors and anaplastic lymphoma kinase inhibitors, new therapeutic strategies are needed to improve clinical outcomes. Immunotherapy through the use of immune checkpoint inhibitors has provided one of the most important breakthroughs in the management of solid tumors, including lung cancers, and has shown promising results in numerous clinical trials. This review will present the current status of immunotherapy for lung cancer and future perspectives on these treatments.

• Journal of Yeungnam Medical Science
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• v.38 no.4
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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.

• Journal of Digestive Cancer Research
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• v.10 no.2
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• pp.65-73
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• 2022

A breakthrough in immunotherapy has changed the outlook for metastatic colorectal cancer (mCRC) treatment as the immune surveillance evasion mechanism of tumor cells has been continuously elucidated. Immune checkpoint inhibitors (ICI), such as pembrolizumab, nivolumab, and ipilimumab, which block immune checkpoint receptors or ligands have been approved for the treatment of mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC based on numerous clinical studies. However, 50% of dMMR/MSI-H mCRC and most mismatch repair proficient/microsatellite stable mCRC remained unresponsive to current immunotherapy. Clinical trials on combination therapy that adds various treatments, such as target agents, chemotherapy, or radiation therapy to ICI, have been actively conducted to overcome this immunotherapy limitation. Further studies on safety and efficacy are needed although several trials presented promising data. Additionally, dMMR/MSI-H, tumor mutation burden, and programmed cell death ligand-1 expression have been studied as biomarkers for predicting the treatment response to immunotherapy, but the discovery and validation of more sensitively predictable biomarkers remained necessary. Thus, this study aimed to review recent studies on immunotherapy in mCRC, summarize the efficacy and limitation of immunotherapy, and describe the biomarkers that predict treatment response.

• Journal of Yeungnam Medical Science
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• v.39 no.1
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• pp.62-66
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• 2022

Immune checkpoint inhibitor (ICI)-associated adrenal insufficiency is rare but may become a serious adverse event in patients treated with ICIs. The present case report documents two cases of adrenal insufficiency developed during chemotherapy plus tislelizumab (百泽安, Baize'an; BeiGene Ltd.) therapy in patients with advanced gastric cancer. Adrenal insufficiency developed after 6 and 13 cycles of treatment and was well controlled with hydrocortisone. The patients also developed hypothyroidism, which was managed with levothyroxine. Two patients showed a partial response, and one patient out of two achieved a near-complete response, sustaining over 11 months. Increased awareness of ICI-related adrenal insufficiency is crucial for early detection and prompt management of patients treated with ICIs.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.3.1-3.20
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• 2020

Immune checkpoint inhibitors (ICIs), including anti-PD-1 and anti-CTLA-4 therapeutic agents, are now approved by the Food and Drug Administration for treatment of various types of cancer. However, the therapeutic efficacy of ICIs varies among patients and cancer types. Moreover, most patients do not develop durable antitumor responses after ICI therapy due to an ephemeral reversal of T-cell dysfunction. As co-stimulatory receptors play key roles in regulating the effector functions of T cells, activating co-stimulatory pathways may improve checkpoint inhibition efficacy, and lead to durable antitumor responses. Here, we review recent advances in our understating of co-stimulatory receptors in cancers, providing the necessary groundwork for the rational design of cancer immunotherapy.

• Genomics & Informatics
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• v.15 no.2
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• pp.56-64
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• 2017

We have previously reported that NS-398, a cyclooxygenase-2 (COX-2)-selective inhibitor, inhibited replicative cellular senescence in human dermal fibroblasts and skin aging in hairless mice. In contrast, celecoxib, another COX-2-selective inhibitor, and aspirin, a non-selective COX inhibitor, accelerated the senescence and aging. To figure out causal factors for the senescence-modulating effect of the inhibitors, we here performed cDNA microarray experiment and subsequent Gene Set Enrichment Analysis. The data showed that several senescence-related gene sets were regulated by the inhibitor treatment. NS-398 up-regulated gene sets involved in the tumor necrosis factor ${\beta}$ receptor pathway and the fructose and mannose metabolism, whereas it down-regulated a gene set involved in protein secretion. Celecoxib up-regulated gene sets involved in G2M checkpoint and E2F targets. Aspirin up-regulated the gene set involved in protein secretion, and down-regulated gene sets involved in RNA transcription. These results suggest that COX inhibitors modulate cellular senescence by different mechanisms and will provide useful information to understand senescence-modulating mechanisms of COX inhibitors.

• BMB Reports
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• v.50 no.6
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• pp.283-284
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• 2017

Single cell transcriptome analysis is a powerful tool for defining cell types or sub-populations within a heterogeneous bulk population. Tumor-associated microenvironment is a complex ecosystem consisting of numerous cell types that support tumor growth, angiogenesis, immune evasion, and metastasis. With the success of checkpoint inhibitors targeting the immune cell compartment, tumor microenvironment is emerging as a potential anti-cancer target, and understanding it has become an imminent subject in cancer biology.

• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.179-189
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• 2019

Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape of lung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensive evidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatment modalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approaches with other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas of active investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosine kinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancer management and keeps expanding its clinical implication. This review will discuss the current position and future role of chemotherapy, and specific consideration for its clinical application in the era of precision medicine.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.207-223
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• 2023

Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.