Stage I non-small cell lung cancer: Treatment modalities, Dutch daily practice and future perspectives

Hopstaken, Jana S.; Ruiter, Julianne Cynthia de; Damhuis, Ronald A.; Langen, Adrianus J de; Diessen, Judi N.A. van; Klomp, Houke M.; Klompenhouwer, Elisabeth G.; Hartemink, Koen J.

doi:10.1016/j.ctarc.2021.100404

Cited by 6 publications

(12 citation statements)

References 61 publications

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“…There are remaining some early-stage NSCLC patients who do not receive surgery because of reasons including poor cardiopulmonary reserve, extremely old age, poor performance status, and personal refusal. Therefore, radiotherapy such as stereotactic ablative radiotherapy (SABR) can be an alternative treatment for early-stage NSCLC patients who are unable to receive surgery [ 90 , 91 ]. Previous studies had shown that local radiation therapy can stimulate the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs).…”

Section: Neoadjuvant and Adjuvant Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

“…At present, several ongoing clinical trials are investigating the use of ICIs with or without chemotherapy as neoadjuvant therapy in resectable NSCLC ( Table 3 .). Several previous early-phase (phases I & II) had shown that ICIs with or without chemotherapy were feasible and effective as a neoadjuvant therapy before surgery [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. Therefore, four main phase III clinical trials (KEYNOTE 617, CheckMate 816, IMpower 030, AEGEAN) are conducted and ongoing now.…”

Section: Neoadjuvant and Adjuvant Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

“…MPR was the endpoint employed most frequently in early-phase trials with neoadjuvant ICIs [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. For early-stage NSCLC, the treatment goal should focus on disease cure and prolonging survival.…”

Section: Future Perspectives: the Challenges Of Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

“…In the design of clinical trials with neoadjuvant ICIs, the neoadjuvant therapies were administrated for 2–4 cycles [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ]. These studies reported that the radiological response assessed by Response Evaluation Criteria in Solid Tumors (RECIST) did not correlate with pathological response [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ]. For example, Forde et al showed that 90% of patients with pathological response in the study ...…”

Section: Future Perspectives: the Challenges Of Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

“…Regarding the HPD of ICIs treatment, NSCLC patients with risk factors may be considered surgery directly followed by adjuvant therapy. Fortunately, no unexpected immune-related adverse event (irAE) that lead to the delay of surgery was reported in these trials with neoadjuvant ICIs in early-stage NSCLC [ 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 ]. In an early trial of neoadjuvant therapy with the combination of nivolumab and ipilimumab in melanoma, 18 of 20 study patients (90%) experienced grade 3 and 4 irAE, and cessation of therapy was required in most patients (17 of 18) [ 141 ].…”

Section: Future Perspectives: the Challenges Of Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

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Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

Chiu

Lin

et al. 2021

Vaccines

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Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized.

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Section: Neoadjuvant and Adjuvant Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

Section: Neoadjuvant and Adjuvant Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

Section: Future Perspectives: the Challenges Of Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

Section: Future Perspectives: the Challenges Of Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

Section: Future Perspectives: the Challenges Of Immunotherapy In Surgically Resectable Nsclcmentioning

confidence: 99%

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Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

Chiu

Lin

et al. 2021

Vaccines

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USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K

Prieto-Garcia

Hartmann²,

Reissland³

et al. 2022

Molecular Oncology

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Oncogenic transformation of lung epithelial cells is a multistep process, frequently starting with the inactivation of tumour suppressors and subsequent development of activating mutations in proto‐oncogenes, such as members of the PI3K or MAPK families. Cells undergoing transformation have to adjust to changes, including altered metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors. Here, we report that the ubiquitin carboxyl‐terminal hydrolase 28 (USP28) enables oncogenic reprogramming by regulating the protein abundance of proto‐oncogenes such as c‐JUN, c‐MYC, NOTCH and ∆NP63 at early stages of malignant transformation. USP28 levels are increased in cancer compared with in normal cells due to a feed‐forward loop, driven by increased amounts of oncogenic transcription factors such as c‐MYC and c‐JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small‐molecule inhibitor resets the proteome of transformed cells towards a ‘premalignant’ state, and its inhibition synergizes with clinically established compounds used to target EGFRL858R‐, BRAFV600E‐ or PI3KH1047R‐driven tumour cells. Targeting USP28 protein abundance at an early stage via inhibition of its activity is therefore a feasible strategy for the treatment of early‐stage lung tumours, and the observed synergism with current standard‐of‐care inhibitors holds the potential for improved targeting of established tumours.

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USP28 enables oncogenic transformation of respiratory cells and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K

Prieto-Garcia

Hartmann

Reissland

et al. 2021

Preprint

View full text Add to dashboard Cite

Oncogenic transformation of lung epithelial cells is a multi-step process, frequently starting with the inactivation of tumor suppressors and subsequent activating mutations in proto-oncogenes, such as members of the PI3K or MAPK family. Cells undergoing transformation have to adjust to changes, such as metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors, which manifest these adjustments. Here, we report that the deubiquitylase USP28 enables oncogenic reprogramming by regulating the protein abundance of proto-oncogenes, such as c-JUN, c-MYC, NOTCH and DNP63, at early stages of malignant transformation. USP28 is increased in cancer compared to normal cells due to a feed-forward loop, driven by increased amounts of oncogenic transcription factors, such as c-MYC and c-JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small molecule inhibitor reset the proteome of transformed cells towards a pre-malignant state, and its inhibition cooperated with clinically established compounds used to target EGFRL858R, BRAFV600E or PI3KH1047R driven tumor cells. Targeting USP28 protein abundance already at an early stage via inhibition of its activity therefore is a feasible strategy for the treatment of early stage lung tumours and the observed synergism with current standard of care inhibitors holds the potential for improved targeting of established tumors.

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Stage I non-small cell lung cancer: Treatment modalities, Dutch daily practice and future perspectives

Cited by 6 publications

References 61 publications

Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

Immunotherapy and Vaccination in Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K

USP28 enables oncogenic transformation of respiratory cells and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K

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