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Immune Checkpoint Inhibitors, Targeted Therapies and Adjuvant Treatment of Lung...
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Immune Checkpoint Inhibitors, Targeted Therapies and Adjuvant Treatment of Lung Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 6483

Special Issue Editor

Dr. Ilaria Attili

E-Mail Website
Guest Editor
Division of Thoracic Oncology, IEO, European Institute of Oncology, IRCCS, Via Ripamonti 435, 20141 Milan, Italy
Interests: EGFR; ALK; ROS1; RET; KRAS; MET; BRAF; HER2; NTRK; PD-L1; NSCLC; lung cancer; immunotherapy; immune checkpoint inhibitors; targeted therapy; tyrosine kinase inhibitors (TKI); resectable; next-generation sequencing; molecular oncology; adjuvant treatment; neoadjuvant treatment; resistance mechanisms; antibody drug conjugates

Special Issue Information

Dear Colleagues,

Advancements in the molecular understanding of lung cancer have swiftly expanded our knowledge of tumor biology, ushering in new horizons for addressing the most lethal cancer globally. Notably, the repertoire of actionable gene alterations, which can potentially serve as therapeutic targets, is rapidly expanding.

Simultaneously, emerging data on the suitability of immunotherapy for lung cancer driven by specific oncogenes emphasize the necessity of comprehensive molecular profiling, including the PD-L1 status, to fine-tune treatment choices. Research into the effectiveness of targeted and immune-based therapies is also extending to early-stage lung cancer, yielding positive outcomes. This evolving knowledge underscores the pressing need for enhanced testing procedures, spanning from early diagnosis to advanced disease, ensuring that patients receive the most suitable therapeutic interventions at any disease stage.

The forthcoming Special Issue will spotlight current insights and forthcoming prospects in tailoring lung cancer treatment through clinical and translational research, with the aim of enhancing patient survival from early to late-stage disease.

Dr. Ilaria Attili
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • lung cancer
  • immunotherapy
  • immune checkpoint inhibitors
  • targeted therapy
  • tyrosine kinase inhibitors (TKI)
  • resectable
  • next-generation sequencing
  • molecular oncology
  • adjuvant treatment

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Published Papers (3 papers)

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Research

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17 pages, 3016 KiB  
Article
Adiponectin Receptor Agonist AdipoRon Inhibits Proliferation and Drives Glycolytic Dependence in Non-Small-Cell Lung Cancer Cells
by Sanober Kafeel, Angela Ragone, Alessia Salzillo, Giuseppina Palmiero, Silvio Naviglio and Luigi Sapio
Cancers 2024, 16(15), 2633; https://doi.org/10.3390/cancers16152633 - 24 Jul 2024
Cited by 1 | Viewed by 855
Abstract
Despite the countless therapeutic advances achieved over the years, non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. To this primacy contribute both non-oncogene addicted and advanced NSCLCs, in which conventional therapies are only partially effective. The adiponectin receptor agonist [...] Read more.
Despite the countless therapeutic advances achieved over the years, non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. To this primacy contribute both non-oncogene addicted and advanced NSCLCs, in which conventional therapies are only partially effective. The adiponectin receptor agonist AdipoRon has revealed antiproliferative action in different cancers, including osteosarcoma and pancreatic cancer. Herein, we investigated its potential anticancer role in NSCLC for the first time. We proved that AdipoRon strongly inhibits viability, growth and colony formation in H1299 and A549 NSCLC cells, mainly through a slowdown in cell cycle progression. Along with the biological behaviors, a metabolic switching was observed after AdipoRon administration in NSCLC cells, consisting of higher glucose consumption and lactate accumulation. Remarkably, both 2-Deoxy Glucose and Oxamate glycolytic-interfering agents greatly enhanced AdipoRon’s antiproliferative features. As a master regulator of cell metabolism, AMP-activated protein kinase (AMPK) was activated by AdipoRon. Notably, the ablation of AdipoRon-induced AMPK phosphorylation by Compound-C significantly counteracted its effectiveness. However, the engagement of other pathways should be investigated afterwards. With a focus on NSCLC, our findings further support the ability of AdipoRon in acting as an anticancer molecule, driving its endorsement as a future candidate in NSCLC therapy. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors, Targeted Therapies and Adjuvant Treatment of Lung Cancer)
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19 pages, 1355 KiB  
Article
Patients with Advanced or Metastasised Non-Small-Cell Lung Cancer with Viscum album L. Therapy in Addition to PD-1/PD-L1 Blockade: A Real-World Data Study
by Friedemann Schad, Anja Thronicke, Ralf-Dieter Hofheinz, Harald Matthes and Christian Grah
Cancers 2024, 16(8), 1609; https://doi.org/10.3390/cancers16081609 - 22 Apr 2024
Viewed by 2632
Abstract
Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA (Viscum album L.) to chemotherapy have shown an association with the improved overall survival of [...] Read more.
Immunotherapy with PD-1/PD-L1 inhibitors has significantly improved the survival rates of patients with metastatic non-small-cell lung cancer (NSCLC). Results of a real-world data study investigating add-on VA (Viscum album L.) to chemotherapy have shown an association with the improved overall survival of patients with NSCLC. We sought to investigate whether the addition of VA to PD-1/PD-L1 inhibitors in patients with advanced or metastasised NSCLC would have an additional survival benefit. In the present real-world data study, we enrolled patients from the accredited national registry, Network Oncology, with advanced or metastasised NSCLC. The reporting of data was performed in accordance with the ESMO-GROW criteria for the optimal reporting of oncological real-world evidence (RWE) studies. Overall survival was compared between patients receiving PD-1/PD-L1 inhibitor therapy (control, CTRL group) versus the combination of anti-PD-1/PD-L1 therapy and VA (combination, COMB group). An adjusted multivariate Cox proportional hazard analysis was performed to investigate variables associated with survival. From 31 July 2015 to 9 May 2023, 415 patients with a median age of 68 years and a male/female ratio of 1.2 were treated with anti-PD-1/PD-L1 therapy with or without add-on VA. Survival analyses included 222 (53.5%) patients within the CRTL group and 193 (46.5%) in the COMB group. Patients in the COMB group revealed a median survival of 13.8 months and patients in the CRTL group a median survival of 6.8 months (adjusted hazard ratio, aHR: 0.60, 95% CI: 0.43–0.85, p = 0.004) after adjustment for age, gender, tumour stage, BMI, ECOG status, oncological treatment, and PD-L1 tumour proportion score. A reduction in the adjusted hazard of death by 56% was seen with the addition of VA (aHR 0.44, 95% CI: 0.26–0.74, p = 0.002) in patients with PD-L1-positive tumours (tumour proportion score > 1%) treated with first-line anti-PD-1/PD-L1 therapy. Our findings suggest that add-on VA correlates with improved survival in patients with advanced or metastasised NSCLC who were treated with PD-1/PD-L1 inhibitors irrespective of age, gender, tumour stage, or oncological treatment. The underlying mechanisms may include the synergistic modulation of the immune response. A limitation of this study is the observational non-randomised study design, which only allows limited conclusions to be drawn and prospective randomised trials are warranted. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors, Targeted Therapies and Adjuvant Treatment of Lung Cancer)
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Review

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14 pages, 274 KiB  
Review
Alectinib vs. Lorlatinib in the Front-Line Setting for ALK-Rearranged Non-Small-Cell Lung Cancer (NSCLC): A Deep Dive into the Main Differences across ALEX and CROWN Phase 3 Trials
by Ilaria Attili, Valeria Fuorivia, Gianluca Spitaleri, Carla Corvaja, Pamela Trillo Aliaga, Ester Del Signore, Riccardo Asnaghi, Ambra Carnevale Schianca, Antonio Passaro and Filippo de Marinis
Cancers 2024, 16(13), 2457; https://doi.org/10.3390/cancers16132457 - 4 Jul 2024
Viewed by 2565
Abstract
Various next-generation ALK TKIs are available as first-line options for ALK-positive NSCLC, with alectinib and lorlatinib being commonly preferred. However, no direct comparison between them has been conducted, making it impossible to pick a winner. We performed an analytic, ‘non-comparative’ assessment of the [...] Read more.
Various next-generation ALK TKIs are available as first-line options for ALK-positive NSCLC, with alectinib and lorlatinib being commonly preferred. However, no direct comparison between them has been conducted, making it impossible to pick a winner. We performed an analytic, ‘non-comparative’ assessment of the two phase 3 pivotal clinical trials showing superiority of alectinib (ALEX) and lorlatinib (CROWN) in comparison to crizotinib. Overall, the two studies were very similar in the study design and patient characteristics, with the exception of the selection and evaluation of brain metastases. PFS hazard ratios numerically favored lorlatinib, both according to the investigator and to BICR. Notably, the 3-year PFS rate was numerically higher with lorlatinib (64%) than with alectinib (46.4%). Despite similar response rates and overall intracranial response, the rate of complete intracranial response was higher with lorlatinib, with a cumulative incidence risk of CNS disease progression at 12 months of 9.4% with alectinib and 2.8% with lorlatinib. The peculiar toxicities of lorlatinib were related to lipidic profile alterations, peripheral oedema and cognitive effects, with no impact on cardiovascular risk nor impairment in quality of life versus crizotinib. Furthermore, the rate of permanent treatment discontinuation due to adverse events was numerically higher with alectinib (26%) than with lorlatinib (7%). In conclusion, despite the immature OS data for both drugs, the efficacy of lorlatinib appears higher than alectinib while maintaining a manageable toxicity profile. Full article
(This article belongs to the Special Issue Immune Checkpoint Inhibitors, Targeted Therapies and Adjuvant Treatment of Lung Cancer)
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