Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer: promise, controversies and ambiguities in the novel treatment paradigm

Breimer, Lars H.; Nousios, Petros; Olsson, Louise; Brunnström, Hans

doi:10.1080/00365513.2020.1742369

Cited by 6 publications

(7 citation statements)

References 78 publications

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Section: Discussionmentioning

confidence: 99%

“…With regards to the association between thyroid dysfunction and the survival outcome in patients with cancer who received PD-1 inhibitors, a previous study revealed that patients with cancer who were treated with pembrolizumab and developed thyroid dysfunction exhibited a higher median OS than those without thyroid dysfunction (40 months vs. 14 months) ( 21 ). Another study indicated that patients with NSCLC and thyroid dysfunction who received PD-1 inhibitors exhibited significantly higher OS and PFS than those without thyroid dysfunction ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

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Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Wu¹,

Wang²,

Bai

et al. 2022

Oncol Lett

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The use of programmed cell death-1 (PD-1) inhibitors has recently been approved in China. As a consequence, the identification of relevant prognostic markers that can assess the efficacy of these compounds is required. Therefore, the present study aimed to explore the incidence of thyroid dysfunction and its ability to predict progression-free survival (PFS) in Chinese patients with cancer who received PD-1 inhibitor treatment. Data from 72 patients with cancer who received treatment with PD-1 inhibitors alone or in combination with chemotherapy or targeted drugs were analyzed. Moreover, the expression levels of free triiodothyronine, thyroxine, and thyrotropin during treatment were assessed to evaluate thyroid dysfunction. A total of 26 (36.1%) patients who had received PD-1 inhibitors developed thyroid dysfunction. Specifically, the incidence of thyroid dysfunction was 35.6% in patients with lung cancer, 25.0% in patients with malignant melanoma, and 46.7% in patients with other types of cancer. In addition, the median PFS was 7.0 (95% confidence interval, 4.9-9.1) months, whereas the 1-and 2-year PFS rates were 35.1 and 26.2%, respectively. Generally, patients with thyroid dysfunction exhibited longer PFS compared with those without thyroid dysfunction (P=0.001). Subgroup analyses were subsequently performed, which demonstrated that thyroid dysfunction was associated with longer PFS in patients with malignant melanoma (P=0.039) and other types of cancer (P=0.002), but not in those with lung cancer (P=0.083). These findings were noted in patients who received PD-1 inhibitor monotherapy (P=0.003), but not PD-1 inhibitor plus chemotherapy (P=0.172) or PD-1 inhibitor plus targeted therapy (P=0.582). Finally, thyroid dysfunction [P=0.001; hazard ratio (HR)=0.260] and PD-1 inhibitor monotherapy (P=0.015; HR=2.231) were identified as independent factors that could predict PFS. In conclusion, the present study demonstrated that thyroid dysfunction during PD-1 inhibitor treatment could be used as a potential marker for the prognosis of favorable PFS in patients with cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Wu¹,

Wang²,

Bai

et al. 2022

Oncol Lett

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“…Distinctive expression pattern of PD-L1 has been shown on different tumor cells and related TME, such as malignant melanoma, NSCLC, ovarian cancer, bladder cancer, breast cancer, renal cell carcinoma, and gastric cancer. [23][24][25][26][27][28][29] In contrast, the difference in efficacy of the PD-1/PD-L1 blockade response might not associate with the expression level of PD-L1. 30 FDA approved membrane staining immunohistochemistry (IHC) assays, including PD-L1 IHC 28-8 phar-mDx, PD-L1 IHC 22C3 pharmDx, VENTANA PD-L1 SP263, and VENTANA PD-L1 SP142 for determining the PD-L1 expression level in different tumors.…”

Section: Pd-l1 As a Biomarker For Cancer Immunotherapymentioning

confidence: 98%

PD‐1/PD‐L1 blockade: Prospectives for immunotherapy in cancer and autoimmunity

Hosseinzadeh

Feizisani²,

Shomali

et al. 2021

IUBMB Life

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Immune checkpoint blockade therapy (ICBT) has become a successful cancer treatment approach in the field of cancer immunotherapy. Blockade of programmed death 1 (PD-1) and programmed death-ligand 1 (PD-L1) with monoclonal antibodies have been known as successful examples of cancer immunotherapy in recent years. Although ICBT has been shown to be beneficial in cancers, such benefits have only been seen in a portion of cancer patients. In this regard, enhancing the therapeutic effects of inhibiting PD-1 and PD-L1 and reducing the side effects of this approach can be considered as

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“…These drugs have now set new standards to the point that ICIs evolved to become first-line treatment [9][10][11][12][13][14] . However, for unknown reasons, an estimated half of the NSCLC patients are refractory to this new modality and the majority become resistant after an initial response [15][16][17][18] .…”

Section: Non-small Cell Lung Cancermentioning

confidence: 99%

RANBP9 as potential therapeutic target in non-small cell lung cancer

Tessari

Soliman

Orlacchio

et al. 2020

JCMT

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Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths in the Western world. Despite progress made with targeted therapies and immune checkpoint inhibitors, the vast majority of patients have to undergo chemotherapy with platinum-based drugs. To increase efficacy and reduce potential side effects, a more comprehensive understanding of the mechanisms of the DNA damage response (DDR) is required. We have shown that overexpressby live cell imaging (Incuyion of the scaffold protein RAN binding protein 9 (RANBP9) is pervasive in NSCLC. More importantly, patients with higher levels of RANBP9 exhibit a worse outcome from treatment with platinum-based drugs. Mechanistically, RANBP9 exists as a target and an enabler of the ataxia telangiectasia mutated (ATM) kinase signaling. Indeed, the depletion of RANBP9 in NSCLC cells abates ATM activation and its downstream targets such as pby live cell imaging (Incuy53 signaling. RANBP9 knockout cells are more sensitive than controls to the inhibition of the ataxia and telangiectasia-related (ATR) kinase but not to ATM inhibition. The absence of RANBP9 renders cells more sensitive to drugs inhibiting the Poly(ADP-ribose)-Polymerase (PARP) resulting in a "BRCAness-like" phenotype. In summary, as a result of increased sensitivity to DNA damaging drugs conferred by its ablation in vitro and in vivo , RANBP9 may be considered as a potential target for the treatment of NSCLC. This article aims to report the results from past and ongoing investigations focused on the role of RANBP9 in the response to DNA damage, particularly in the context of NSCLC. This review concludes with future directions and speculative remarks which will need to be addressed in the coming years.

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Immune checkpoint inhibitors of the PD-1/PD-L1-axis in non-small cell lung cancer: promise, controversies and ambiguities in the novel treatment paradigm

Cited by 6 publications

References 78 publications

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

Thyroid dysfunction during PD‑1 inhibitor treatment in patients with cancer: Incidence and association with progression‑free survival

PD‐1/PD‐L1 blockade: Prospectives for immunotherapy in cancer and autoimmunity

RANBP9 as potential therapeutic target in non-small cell lung cancer

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