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Advances in Metastatic Non-small Cell Lung Cancer–Implications on Diagnosis and...
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Advances in Metastatic Non-small Cell Lung Cancer–Implications on Diagnosis and Treatment as We Head towards 2024

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

Deadline for manuscript submissions: 31 May 2024 | Viewed by 4614

Special Issue Editors

Dr. Nagashree Seetharamu

E-Mail Website
Guest Editor
Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY 11549, USA
Interests: non-small cell lung cancer; predictive and prognostic biomarkers in lung cancers; immuno-oncology; precision medicine; health related quality of life; drug toxicity; patient-reported outcomes; health care disparities
Dr. Morana Vojnic

E-Mail Website
Guest Editor
Northwell Health Cancer Institute, Lenox Hill Hospital, New York, NY 10021, USA
Interests: lung cancer; brain metastases; leptomeningeal disease; translational research

Special Issue Information

Dear Colleagues,

Non-small-cell lung cancer (NSCLC) has the highest cancer-related mortality rate worldwide to this day. Oncogenes, tumor heterogeneity and variabilities in the tumor microenvironment may all contribute to cancer progression and metastases, with >50% being metastatic at diagnosis (mainly brain, bone, liver, and adrenal glands). 

In the past decade, advances in identifying driver mutations have completely changed the therapeutic landscape of this disease. Targeted therapies such as osimertinib and other small-molecule tyrosine kinase inhibitors, are now widely used in clinical practice. At the same time, new therapeutic targets are also emerging, greatly extending the life expectancy of patients who carry these alterations. Immunotherapy has also significantly improved the prognosis and survival of NSCLC patients, even for traditionally frail patients who are not candidates for chemotherapy. We are increasingly able to apply the concept of “precision oncology” in our clinics today and focus on delivering therapies to our patients that are individualized to their specific needs. 

This Special Issue aims to publish high-quality research and reviews on the pathogenesis and evolving treatment landscape (immunotherapy, targeted therapy, etc.) of metastatic NSCLC with a joint mission of combating this deadly cancer.

Dr. Nagashree Seetharamu
Dr. Morana Vojnic
Guest Editors

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. 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

  • NSCLC
  • oncogene
  • metastases
  • targeted therapy
  • immunotherapy
  • pathogenesis

Published Papers (3 papers)

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Research

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18 pages, 3572 KiB  
Article
Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations
by Yusuke Tomita, Shinya Sakata, Kosuke Imamura, Shinji Iyama, Takayuki Jodai, Koichi Saruwatari, Shohei Hamada, Kimitaka Akaike, Moriyasu Anai, Kazuaki Fukusima, Akira Takaki, Hirotake Tsukamoto, Yoshihiko Goto, Chihiro Motozono, Kenji Sugata, Yorifumi Satou, Takamasa Ueno, Tokunori Ikeda and Takuro Sakagami
Cancers 2024, 16(1), 47; https://doi.org/10.3390/cancers16010047 - 21 Dec 2023
Cited by 1 | Viewed by 1571
Abstract
The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI [...] Read more.
The gut microbiota has emerged as a key regulator of immune checkpoint inhibitor (ICI) efficacy. Therapeutic approaches aimed at manipulating the microbiota through targeted reconstitution to enhance cancer treatment outcomes have garnered considerable attention. A single live microbial biotherapeutic bacterium, Clostridium butyricum MIYAIRI 588 strain (CBM588), has been shown to enhance the effects of ICI monotherapy in patients with advanced lung cancer. However, whether CBM588 affects the outcomes of chemoimmunotherapy combinations in lung cancer remains unknown. We hypothesized that CBM588 augments the effect of chemoimmunotherapy combinations and restores diminished effectiveness in patients with non-small cell lung cancer (NSCLC) receiving dysbiosis-inducing drugs. To validate this hypothesis, we retrospectively analyzed 106 patients with stage IV or recurrent metastatic NSCLC consecutively treated with chemoimmunotherapy combinations. A survival analysis was performed employing univariate and multivariate Cox proportional hazard models with inverse probability of treatment weighting (IPTW) using propensity scores. Forty-five percent of patients received Clostridium butyricum therapy. CBM588 significantly extended overall survival in patients with NSCLC receiving chemoimmunotherapy. The favorable impact of CBM588 on the efficacy of chemoimmunotherapy combinations varied based on tumor-programmed cell death ligand 1 (PD-L1) expression. The survival benefit of CBM588 in the PD-L1 <1% cohort was higher than that in the PD-L1 1–49% and PD-L1 ≥ 50% cohorts. Furthermore, CBM588 was associated with improved overall survival in patients receiving proton pump inhibitors and/or antibiotics. CBM588-induced manipulation of the commensal microbiota holds the potential to enhance the efficacy of chemoimmunotherapy combinations, warranting further exploration of the synergy between CBM588 and immunotherapy. Full article
(This article belongs to the Special Issue Advances in Metastatic Non-small Cell Lung Cancer–Implications on Diagnosis and Treatment as We Head towards 2024)
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14 pages, 482 KiB  
Article
Epidermal Growth Factor Receptor T790M Mutation Testing in Non-Small Cell Lung Cancer: An International Collaborative Study to Assess Molecular EGFR T790M Testing in Liquid Biopsy
by Martin Filipits, Verena Kainz, Viktor Sebek, Herwig Zach and on behalf of the Liquid Biopsy Collaborative Study Group
Cancers 2023, 15(13), 3528; https://doi.org/10.3390/cancers15133528 - 07 Jul 2023
Cited by 1 | Viewed by 1269
Abstract
Background: The detection of the EGFR T790M (T790M) mutation in non-small cell lung cancer (NSCLC) patients who progressed under treatment with first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) is important to offer a subsequent therapy with a third-generation EGFR-TKI. Liquid biopsy is a [...] Read more.
Background: The detection of the EGFR T790M (T790M) mutation in non-small cell lung cancer (NSCLC) patients who progressed under treatment with first- or second-generation EGFR-tyrosine kinase inhibitors (TKIs) is important to offer a subsequent therapy with a third-generation EGFR-TKI. Liquid biopsy is a powerful tool to determine the T790M mutation status. Several liquid biopsy platforms with varying degrees of accuracy are available to test for T790M mutations, and sensitivities may differ among these methods. Methods: As no standard exists for the testing of T790M mutation in liquid biopsy, we performed a collaborative study to describe and compare the sensitivity of different in-house liquid biopsy platforms for the detection of the T790M mutation, EGFR exon 19 deletion (del19) and EGFR L858R mutation (L858R) across multiple participating laboratories in seven Central and Eastern European countries. Results: Of the 25 invited laboratories across Central and Eastern Europe, 21 centers participated and received 10 plasma samples spiked with cell-line DNA containing the T790M, del19, or L858R mutation in different concentrations. In-house PCR-based and NGS-based methods were used accordingly, and results were reported as in routine clinical practice. Two laboratories, which used the AmoyDx® EGFR 29 Mutations Detection Kit (AmoyDx) with Cobas® cfDNA Sample Preparation Kit and QX200 Droplet Digital PCR (ddPCR) with the QIAamp Circulating Nucleic Acid Kit identified all ten samples correctly. Cobas® EGFR Mutation Test v2 (Cobas), the NGS methods, and the IdyllaTM detection method used in this study performed within the known sensitivity range of each detection method. Conclusions: If a negative result was obtained from methods with lower sensitivity (e.g., Cobas), repeated liquid biopsy testing and/or tissue biopsy analysis should be performed whenever possible, to identify T790M-positive patients to allow them to receive the optimal second-line treatment with a third-generation EGFR TKI. Full article
(This article belongs to the Special Issue Advances in Metastatic Non-small Cell Lung Cancer–Implications on Diagnosis and Treatment as We Head towards 2024)
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Review

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16 pages, 9633 KiB  
Review
Targeted Therapies for Kirsten Rat Sarcoma (KRAS) G12C Mutant Metastatic Non-Small-Cell Lung Cancers
by Cian O’Leary, Grace Murphy, Yong Yeung, Ming Tang, Vikram Jain and Connor G O’Leary
Cancers 2023, 15(23), 5582; https://doi.org/10.3390/cancers15235582 - 25 Nov 2023
Cited by 2 | Viewed by 1162
Abstract
Non-small-cell lung cancer (NSCLC) is a prevalent and often fatal malignancy. Advancements in targeted therapies have improved outcomes for NSCLC patients in the last decade. Kirsten rat sarcoma virus (KRAS) is a commonly mutated oncogene in NSCLC, contributing to tumorigenesis and proliferation. Though [...] Read more.
Non-small-cell lung cancer (NSCLC) is a prevalent and often fatal malignancy. Advancements in targeted therapies have improved outcomes for NSCLC patients in the last decade. Kirsten rat sarcoma virus (KRAS) is a commonly mutated oncogene in NSCLC, contributing to tumorigenesis and proliferation. Though classically difficult to target, recently developed KRAS G12C inhibitors (sotorasib and adagrasib) have now overcome this therapeutic hurdle. We discuss the evidence for these medications, their pitfalls and adverse effects, as well as future directions in this space. Though these medications demonstrate substantial response rates in a heavily pre-treated advanced NSCLC cohort, as phase-3 evidence does not yet demonstrate an overall survival benefit versus standard-of-care chemotherapy, docetaxel. Additionally, these medications appear to have a negative interaction in combination with immunotherapies, with substantially greater hepatotoxicity rates observed. Despite this, it is undeniable that these medications represent an important advancement in targeted and personalised oncological treatment. Current and future trials assessing these medications in combination and through sequencing strategies will likely yield further clinically meaningful outcomes to guide treatment in this patient cohort. Full article
(This article belongs to the Special Issue Advances in Metastatic Non-small Cell Lung Cancer–Implications on Diagnosis and Treatment as We Head towards 2024)
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