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Biomedicines
Special Issues
Mechanism and Novel Therapeutic Approaches for Non-small Cell Lung Cancer
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Mechanism and Novel Therapeutic Approaches for Non-small Cell Lung Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 3356

Special Issue Editor

Dr. Dan Yan

E-Mail Website
Guest Editor
Affiliation Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University, Atlanta, GA 30322, USA
Interests: TAM (Tyro3; Axl; MERTK) receptor kinases; EGFR mutation; KRAS mutation; non-small-cell lung cancer; immunotherapy and combination therapy

Special Issue Information

Dear Colleagues,

The immune system is meant to recognize and destroy malignant cells. However, tumors evolve to evade host immune defenses through various mechanisms. It has been shown that immunotherapy, as a promising treatment option for advanced lung cancer, could help the immune system to better identify and kill cancer cells, although only 15-20% of patients achieve lasting benefit. Biomarkers should urgently be identified, and we need to better understand the mechanisms related with primary or secondary resistance.

Kirsten rat sarcoma proto-oncogene (KRAS) was considered to be an “undruggable” target until recently, when the FDA granted accelerated approval for sotorasib, a KRAS G12C selective small-molecule inhibitor, for the treatment of advanced non-small-cell lung cancer (NSCLC) patients harboring with a KRAS G12C mutation. A better understanding of the biology of the protein in combination with novel technologies meant that this once seemingly impossible goal of a KRAS inhibitor became reality. In addition, several other druggable oncogenes have been uncovered, and targeted drugs have been developed after advanced molecular biology studies, including EGFR-selective receptor tyrosine kinase inhibitors. They prolong the survival time in patients with NSCLC. However, acquired resistance is an unmet problem.

This Special Issue will highlight current advancements in immunotherapy and targeted therapies in lung cancer, especially in non-small-cell lung cancer. We welcome both preclinical and clinical studies with findings that lead to better understanding of this rapidly evolving field.

Dr. Dan Yan
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 short 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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • non-small-cell lung cancer
  • immunotherapy
  • immune checkpoint inhibitor
  • receptor tyrosine kinase
  • EGFR mutation
  • KRAS mutation
  • small-molecule inhibitor

Published Papers (2 papers)

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Research

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7 pages, 1083 KiB  
Communication
Prognostic Associations of Concomitant Antibiotic Use in Patients with Advanced NSCLC Treated with Atezolizumab: Sensitivity Analysis of a Pooled Investigation of Five Randomised Control Trials
by Arkady T Manning-Bennett, Julie Cervesi, Pierre-Alain Bandinelli, Michael J Sorich and Ashley M Hopkins
Biomedicines 2023, 11(2), 528; https://doi.org/10.3390/biomedicines11020528 - 11 Feb 2023
Viewed by 1515
Abstract
Background: Immune checkpoint inhibitors (ICIs) have been a significant milestone for the treatment of advanced non-small cell lung cancer (NSCLC). However, the efficacy of ICIs can vary substantially between patients, with disparities in treatment outcomes being potentially driving by changes in the microbiome. [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) have been a significant milestone for the treatment of advanced non-small cell lung cancer (NSCLC). However, the efficacy of ICIs can vary substantially between patients, with disparities in treatment outcomes being potentially driving by changes in the microbiome. Antibiotics can cause dysbiosis and are hypothesised to impact the efficacy of ICIs Methods: Data were pooled from five randomised clinical control trials, IMpower130, IMpower131, IMpower150, OAK, and POPLAR, assessing atezolizumab in advanced NSCLC. Cox proportional hazard models were used to determine whether antibiotic use within 6-weeks before and after randomisation was associated with progression-free survival (PFS) and overall survival (OS) outcomes, with data further stratified by programmed death ligand-1 (PD-L1) status. Results: Antibiotic use was significantly associated with worsened PFS (hazard ratio (HR) = 1.19 [1.08–1.30], p ≤ 0.001) and OS (HR = 1.27 [1.13–1.42], p ≤ 0.001) in patients treated with atezolizumab and those not treated with atezolizumab (PFS, HR = 1.21 [1.08–1.36] p < 0.001, OS, HR = 1.33 [1.16–1.51] p < 0.001). These associations were relatively consistent in both PD-L1 positive and PD-L1 negative. Conclusions: Antibiotic use within a ±6-week window was significantly associated with worse PFS and OS. Full article
(This article belongs to the Special Issue Mechanism and Novel Therapeutic Approaches for Non-small Cell Lung Cancer)
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Review

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15 pages, 368 KiB  
Review
Hope and Challenges: Immunotherapy in EGFR-Mutant NSCLC Patients
by Dan Yan
Biomedicines 2023, 11(11), 2916; https://doi.org/10.3390/biomedicines11112916 - 28 Oct 2023
Cited by 1 | Viewed by 1506
Abstract
EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. Sadly, remission is transient, and no approved effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Although immunotherapy with immune checkpoint [...] Read more.
EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for non-small cell lung cancer (NSCLC) patients harboring sensitive EGFR mutations. Sadly, remission is transient, and no approved effective treatment options are available for EGFR-TKI-advanced EGFR-mutant NSCLCs. Although immunotherapy with immune checkpoint inhibitors (ICIs) induces sustained cancer remission in a subset of NSCLCs, ICI therapy exhibits limited activity in most EGFR-mutant NSCLCs. Mechanistically, the strong oncogenic EGFR signaling in EGFR-mutant NSCLCs contributes to a non-inflamed tumor immune microenvironment (TIME), characterized by a limited number of CD8+ T cell infiltration, a high number of regulatory CD4+ T cells, and an increased number of inactivated infiltrated T cells. Additionally, EGFR-mutant NSCLC patients are generally non-smokers with low levels of PD-L1 expression and tumor mutation burden. Promisingly, a small population of EGFR-mutant NSCLCs still durably respond to ICI therapy. The hope of ICI therapy from pre-clinical studies and clinical trials is reviewed in EGFR-mutant NSCLCs. The challenges of application ICI therapy in EGFR-mutant NSCLCs are also reviewed. Full article
(This article belongs to the Special Issue Mechanism and Novel Therapeutic Approaches for Non-small Cell Lung Cancer)
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