Development and clinical applications of cancer immunotherapy against PD-1 signaling pathway

Wakabayashi, Grace; Lee, Yu Ching; Luh, Frank; Kuo, Chun Nan; Chang, Wei Chao; Yen, Yun

doi:10.1186/s12929-019-0588-8

Cited by 33 publications

(26 citation statements)

References 110 publications

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“…In recent years, immune checkpoint inhibition has been considered as a novel treatment method (29). PD-1 is one of the immune checkpoints responsible for regulating the immune response.…”

Section: Discussionmentioning

confidence: 99%

CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma

Song

et al. 2020

Front. Oncol.

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T-lymphoblastic lymphoma (T-LBL) is a rare hematological malignancy with highly aggressive, unique clinical manifestations, and poor prognosis. Cell division cycle 27 (CDC27) was previously reported to be a significant subunit of the anaphase-promoting complex/cyclosome. However, the specific functions and relevant mechanisms of CDC27 in T-LBL remain unknown. Through immunohistochemistry staining, we identified that CDC27 was overexpressed in T-LBL tissues and related to tumor progression and poor survival. Functional experiments demonstrated that CDC27 promoted proliferation in vivo and in vitro. Further experiment suggested the role of CDC27 in facilitating G1/S transition and promoting the expression of Cyclin D1 and CDK4. Then the effect of CDC27 in inhibiting apoptosis was also identified. Furthermore, we found a positive correlation between the expression of CDC27 and Programmed death ligand-1 (PD-L1) by immunohistochemistry staining. The interaction between CDC27 and PD-L1 was also proved by western blot, luciferase gene reporter assay and immunofluorescence. Taken together, our results showed that CDC27 contributes to T-LBL progression and there is a positive correlation between PD-L1 and CDC27, which offers novel perspectives for future studies on targeting CDC27 in T-LBL.

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“…In recent years, immune checkpoint inhibition has been considered as a novel treatment method (29). PD-1 is one of the immune checkpoints responsible for regulating the immune response.…”

Section: Discussionmentioning

confidence: 99%

CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma

Song

et al. 2020

Front. Oncol.

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“…For ICIs, some predictive biomarkers have been strongly associated with the response to such therapy with monoclonal antibodies. These include, PD-L1 in NSCLC and advanced urothelial carcinoma patients treated with pembrolizumab ( 130 , 131 ), tumor mutation burden ( 132 ), and MSI-H/dMMR in patients with pembrolizumab for unresectable or metastatic mismatch-repair deficient solid tumors ( 133 ). Multiple studies have proposed the absolute lymphocyte count and lactate dehydrogenase in peripheral blood as potential predictive biomarkers.…”

Section: Predictive Indicators For Combination Therapy Of Anti-angiogmentioning

confidence: 99%

Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment

et al. 2020

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Advances in cancer immunity have promoted a major breakthrough in the field of cancer therapy. This is mainly associated with the successful development of immune checkpoint inhibitors (ICIs) for multiple types of human tumors. Blockade with different ICIs, including programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, may activate the immune system of the host against malignant cells. However, only a subgroup of patients with cancer would benefit from immune checkpoint blockade. Some patients experience primary resistance to initial immunotherapy, and a majority eventually develop acquired resistance to ICIs. However, the mechanisms involved in the development of drug resistance to immune checkpoint blockade remain unclear. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for overcoming the low efficacy of ICIs. Moreover, through their direct anti-cancer effect by inhibiting tumor growth and metastasis, anti-angiogenic drugs reprogram the tumor milieu from an immunosuppressive to an immune permissive microenvironment. Activated immunity by immune checkpoint blockade also facilitates anti-angiogenesis by downregulating the expression of vascular endothelial growth factor and alleviating hypoxia condition. Many clinical trials showed an improved anti-cancer efficacy and prolonged survival following the addition of anti-angiogenic agents to ICIs. This review summarizes the current understanding and clinical development of combination therapy with immune checkpoint blockade and anti-angiogenic strategy.

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“…Identifying predictive biomarkers for checkpoint blockade response is critical for optimizing treatment efficacy and preventing drug-related toxic effects. These inhibitors have been associated with improved survival and fewer adverse events compared with chemotherapy for various tumor types, including metastatic melanoma, advanced non-small cell lung cancer (NSCLC), and head and neck squamous cell carcinoma [29,30]. Molecular diagnostics have been approved for the use of anti-PD-1/anti-PD-L1 therapies, particularly for pembrolizumab, nivolumab, and atezolizumab [31].…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000–2020)

Kim

Ceccarelli

2021

JPM

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Pharmacogenomics (PGx) is a key subset of precision medicine that relates genomic variation to individual response to pharmacotherapy. We assessed longitudinal trends in US FDA approval of new drugs labeled with PGx information. Drug labels containing PGx information were obtained from Drugs@FDA and guidelines from PharmGKB were used to compare the actionability of PGx information in drug labels across therapeutic areas. The annual proportion of new drug approvals with PGx labeling has increased by nearly threefold from 10.3% (n = 3) in 2000 to 28.2% (n = 11) in 2020. Inclusion of PGx information in drug labels has increased for all clinical areas over the last two decades but most prominently for cancer therapies, which comprise the largest proportion (75.5%) of biomarker–drug pairs for which PGx testing is required. Clinically actionable information was more frequently observed in biomarker–drug pairs associated with cancer drugs compared to those for other therapeutic areas (n = 92 (59.7%) vs. n = 62 (40.3%), p < 0.0051). These results suggest that further evidence is needed to support the clinical adoption of pharmacogenomics in non-cancer therapeutic areas.

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Development and clinical applications of cancer immunotherapy against PD-1 signaling pathway

Cited by 33 publications

References 110 publications

CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma

CDC27 Promotes Tumor Progression and Affects PD-L1 Expression in T-Cell Lymphoblastic Lymphoma

Anti-angiogenic Agents in Combination With Immune Checkpoint Inhibitors: A Promising Strategy for Cancer Treatment

Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000–2020)

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