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Target and Im-Oncology Therapeutic Approaches for Lung Cancer

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Pulmonology".

Deadline for manuscript submissions: closed (25 April 2023) | Viewed by 28158

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Special Issue Editors

Prof. Dr. Shun Lu

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Guest Editor

Department of Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
Interests: lung cancer; targeted therapy; Im-oncology therapy

Prof. Dr. Yongfeng Yu

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Guest Editor

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China
Interests: lung cancer; targeted therapy; Im-oncology therapy

Special Issue Information

Dear Colleagues,

Lung cancer is the most frequent cause of cancer-related deaths worldwide. Every year, 1.8 million people are diagnosed with lung cancer, and 1.6 million people die as a result of the disease. Five-year survival rates vary from 4 to 17% depending on stage and regional differences.

Recognition that lung cancer is primarily a disease of the genome has fueled recent focus on the development of more personalized or precision treatments based on genomic information. Lung cancer can thus be subdivided into clinically relevant molecular subsets, including EGFR, ALK, ROS1, HER2, BRAF, KRAS, RET, MET, and so on. Targeted therapy could lead to substantial outcome improvements. Meanwhile, unprecedented advances have been made in lung cancer treatment with the use of immunotherapy. However, limited responses to a subset of patients, drug resistance, and treatment-related adverse events are still unsolved. The scope of this Special Issue is to provide an overview of recent advances in the field of targeted therapy and immunotherapy for lung cancer. Therefore, researchers in this field are encouraged to submit an original article or review to this Special Issue (case reports and short reviews are not accepted).

Prof. Dr. Shun Lu
Prof. Dr. Yongfeng Yu
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. Journal of Clinical Medicine 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 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

lung cancer
targeted therapy
immunotherapy
drug resistance
biomarkers
adverse events
tumor heterogeneity
immune microenvironment

Published Papers (12 papers)

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Research

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14 pages, 7238 KiB

Open AccessArticle

Landscape and Predictive Significance of the Structural Classification of EGFR Mutations in Chinese NSCLCs: A Real-World Study

by Linping Gu, Huayan Huang, Zhangwendi Xu, Xiaomin Niu, Ziming Li, Liliang Xia, Yongfeng Yu and Shun Lu

J. Clin. Med. 2023, 12(1), 236; https://doi.org/10.3390/jcm12010236 - 28 Dec 2022

Cited by 3 | Viewed by 1637

Abstract

Background: Non-classical EGFR mutations demonstrate heterogeneous and attenuated responsiveness to EGFR TKIs. Non-small cell lung cancer (NSCLC) patients with atypical EGFR mutations have limited therapeutic options. A recent study established a novel structural-based classification of EGFR mutations and showed its value in predicting the response to TKI. We sought to interrogate the distribution of different structural types and to validate the predictive value in Chinese NSCLCs. Methods: A total of 837 tumor samples were retrospectively recruited from 522 patients with unresectable EGFR-mutant NSCLC. EGFR mutations were classified into four groups: classical-like, T790M-like, Ex20ins-L, and PACC. Treatment information and clinical outcomes were obtained from 436 patients. The time to treatment failure (TTF) was determined on a per-sample basis. Results: Of the 837 EGFR-mutant samples, 67.9%, 18.5%, 9.0%, and 3.1% harbored classical-like, T790M-like, PACC, and Ex20ins-L mutations, respectively. Thirteen (1.6%) samples carried mutations beyond the four types. Among the 204 samples with atypical mutations, 33.8%, 36.7%, 12.7%, and 10.3% were classical-like, PACC, Ex20ins-L, and T790M-like, respectively. In patients with PACC mutations, second-generation TKIs demonstrated a significantly longer TTF than first-generation TKIs (first-line: 15.3 vs. 6.2 months, p = 0.009; all-line: 14.7 vs. 7.1 months, p = 0.003), and a trend of longer TTF than third-generation TKIs (all-line: 14.7 vs. 5.1 months, p = 0.135). Conclusions: Our study depicted the landscape of structural types of EGFR mutations in Chinese NSCLC patients. Our results also suggest that the structural classification can serve as a predictive marker for the efficacy of various EGFR TKIs, which would guide therapeutic decision making. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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16 pages, 8755 KiB

Open AccessArticle

T Cell-Mediated Tumor Killing-Related Classification of the Immune Microenvironment and Prognosis Prediction of Lung Adenocarcinoma

by Peng Ding, Lichao Liu, Yawen Bin, Yu Huang, Lingjuan Chen, Lu Wen, Ruiguang Zhang, Fan Tong and Xiaorong Dong

J. Clin. Med. 2022, 11(23), 7223; https://doi.org/10.3390/jcm11237223 - 05 Dec 2022

Cited by 1 | Viewed by 1357

Abstract

Background: Although immune checkpoint inhibitors (ICI) are a promising therapeutic strategy for lung adenocarcinoma (LUAD), individual subgroups that might benefit from them are yet to be identified. As T cell-mediated tumor killing (TTK) is an underlying mechanism of ICI, we identified subtypes based on genes associated with TTK sensitivity and assessed their predictive significance for LUAD immunotherapies. Methods: Using high-throughput screening techniques, genes regulating the sensitivity of T cell-mediated tumor killing (GSTTK) with differential expression and associations with prognosis were discovered in LUAD. Furthermore, patients with LUAD were divided into subgroups using unsupervised clustering based on GSTTK. Significant differences were observed in the tumor immune microenvironment (TIME), genetic mutation and immunotherapy response across subgroups. Finally, the prognostic significance of a scoring algorithm based on GSTTK was assessed. Results: A total of 6 out of 641 GSTTK exhibited differential expression in LUAD and were associated with prognosis. Patients were grouped into two categories based on the expression of the six GSTTK, which represented different TTK immune microenvironments in LUAD. Immune cell infiltration, survival difference, somatic mutation, functional enrichment and immunotherapy responses also varied between the two categories. Additionally, a scoring algorithm accurately distinguished overall survival rates across populations. Conclusions: TTK had a crucial influence on the development of the varying TIME. Evaluation of the varied TTK modes of different tumors enhanced our understanding of TIME characteristics, wherein the changes in T cell activity in LUAD are reflected. Thus, this study guides the development of more effective therapeutic methods. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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13 pages, 4655 KiB

Open AccessArticle

The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer

by Lingling Zu, Jinling He, Ning Zhou, Jingtong Zeng, Yifang Zhu, Quanying Tang, Xin Jin, Lei Zhang and Song Xu

J. Clin. Med. 2022, 11(21), 6421; https://doi.org/10.3390/jcm11216421 - 29 Oct 2022

Cited by 7 | Viewed by 2166

Abstract

Integrins are involved in extracellular and intracellular signaling and are often aberrantly expressed in tumors. Integrin beta 2 (ITGB2) has previously been demonstrated to be correlated with the host defense. However, the expression profile and role of ITGB2 in non-small-cell lung cancer (NSCLC) remain unclear. Here, we found that the genetic alterations in ITGB2 was predominated by gene mutation and copy number deletion using cBioPortal analysis, and its expression was downregulated in the NSCLC tissues, as validated by the UALCAN, TCGA, and GEO databases and our tissue samples. Kaplan–Meier (KM) plotter analysis revealed that patients with a lower ITGB2 expression had a shorter overall survival (OS) time (p = 0.01). Moreover, 1089 differentially expressed genes (DEGs) in the NSCLC tissues were screened using the TCGA database. The GO and KEGG enrichment analysis showed that the DEGs were closely associated with immune processes and cell adhesion. The protein–protein interaction (PPI) network revealed that 10 of 15 EMT-related genes among the DEGs might lead to the metastasis of NSCLC. Concomitantly, the expression of ITGB2 was positively correlated with the infiltration of Treg cells and Myeloid-derived suppressor cells (MDSC). Biologically, the ectopic expression of ITGB2 significantly inhibited the proliferation and metastasis of NSCLC cells. Mechanistically, we demonstrated that ITGB2 suppressed the expression of N-cadherin, Vimentin, Slug, Snail, and Twist, while it promoted E-cadherin expression, according to gain-of-function studies. In conclusion, ITGB2 can inhibit the proliferation and migration of NSCLC cells, leading to a poor prognosis, via epithelial–mesenchymal transition (EMT) signaling. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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15 pages, 3086 KiB

Open AccessArticle

Decreased Tertiary Lymphoid Structures in Lung Adenocarcinomas with ALK Rearrangements

by Yi Zou, Jing Zhao, Fengbo Huang, Xueping Xiang and Yang Xia

J. Clin. Med. 2022, 11(19), 5935; https://doi.org/10.3390/jcm11195935 - 08 Oct 2022

Cited by 2 | Viewed by 1887

Abstract

Purpose: This study sought to characterize the tumor immune microenvironment (TIME) of lung adenocarcinomas with ALK rearrangements (ALK+ LUAD), which responds poorly to immune checkpoint inhibitors (ICIs) therapy. Materials and methods: Immune score evaluation and immunohistochemical (IHC) validation of B cells, cytotoxic, helper, regulatory T cells, dendritic cells, and tumor-associated macrophages were performed on the TCGA cohort and the whole tissue sections of our matched surgical samples, respectively, between ALK+ and ALK− LUAD. The formation and spatial organization of TLS, intra- and extra-TLS immune cell features, and tumor PD-L1 expression were analyzed independently. Results: Immune scores and TLS-signature gene levels were found to be lower in ALK+ TCGA LUAD. Quantitative IHC comparison confirmed the lower densities of TLS (0.10/mm² vs. 0.34/mm², p = 0.026) and intra-TLS immune cells (CD4+ helper T cells: 57.65/mm² vs. 274.82/mm², p = 0.026; CD8+ cytotoxic T cells: 22.46/mm² vs. 172.83/mm², p = 0.018; and CD20+ B cells: 36.08/mm² vs. 207.29/mm², p = 0.012) in ALK+ surgical samples. The TLS formation was negatively correlated with tumor progression in ALK+ tumors. The proportion of intra-TLS CD8+ cytotoxic T cells was the independent protective factors of node metastasis (HR: 0.599, 95% CI: 0.414–0.868, p = 0.007), and the density of intra-TLS CD20+ B cells was the independent protective factor of pStage (HR: 0.641, 95% CI: 0.446–0.922, p = 0.016). Tumors with intratumoral TLS showed significantly higher expression of PD-L1 (p = 0.029). Conclusion: ALK+ LUAD harbored a cold TIME featured by decreased TLS formation, which closely correlated to tumor progression and might contribute to the poor efficiency of ICIs. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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14 pages, 1488 KiB

Open AccessArticle

Composition of the Gut Microbiota Associated with the Response to Immunotherapy in Advanced Cancer Patients: A Chinese Real-World Pilot Study

by Xi Cheng, Jiawei Wang, Liu Gong, Yong Dong, Jiawei Shou, Hongming Pan, Zhaonan Yu and Yong Fang

J. Clin. Med. 2022, 11(18), 5479; https://doi.org/10.3390/jcm11185479 - 18 Sep 2022

Cited by 5 | Viewed by 2059

Abstract

Background: The composition of the gut microbiota is associated with the response to immunotherapy for different cancers. However, the majority of previous studies have focused on a single cancer and a single immune checkpoint inhibitor. Here, we investigated the relationship between the gut microbiota and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced cancers. Method: In this comprehensive study, 16S rRNA sequencing was performed on the gut microbiota of pre-immunotherapy and post-immunotherapy, of 72 advanced cancer patients in China. Results: At the phylum level, Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the main components of the microbiota in the 72 advanced cancer patients. At the genus level, Bacteroides and Prevotella were the dominant microbiota among these 72 patients. The PD_whole_tree, Chao1, Observed_species and Shannon indices of R.0 and R.T were higher than those of NR.0 and NR.T. The results of LEfSe showed that Archaea, Lentisphaerae, Victivallaceae, Victivallales, Lentisphaeria, Methanobacteriaceae, Methanobacteria, Euryarchaeota, Methanobrevibacter, and Methanobacteriales were significantly enriched in the response group before immunotherapy (R.0), and the Clostridiaceae was significantly enriched in the non-response group before immunotherapy (NR.0) (p < 0.05). Lachnospiraceae and Thermus were significantly enriched in the response group after immunotherapy (R.T), and Leuconostoc was significantly enriched in R.0 (p < 0.05). ROC analysis showed that the microbiota of R.T (AUC = 0.70) had obvious diagnostic value in differentiating Chinese cancer patients based on their response to immunotherapy. Conclusions: We demonstrated that the gut microbiota was associated with the clinical response to anti-PD-1 immunotherapy in cancer patients. Taxonomic signatures enriched in responders were effective biomarkers to predict the clinical response. Our findings provide a new strategy to improve the efficiency of responses to immunotherapy among cancer patients. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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13 pages, 570 KiB

Open AccessArticle

Treating with Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) Accompanying Lower Incidence of Second Primary Cancers

by Wen-Ru Chou, Ben-Chang Shia, Yen-Chun Huang, Chieh-Wen Ho and Mingchih Chen

J. Clin. Med. 2022, 11(17), 5222; https://doi.org/10.3390/jcm11175222 - 04 Sep 2022

Cited by 1 | Viewed by 1131

Abstract

Lung cancer survivors are at risk of developing second primary cancers (SPCs). Although some risk factors for the development of SPCs have been addressed, their impacts have not been clarified. This study, based on Taiwan’s National Health Insurance Research Database (NHIRD), a nationwide database, was designed to investigate the risk factors for SPCs in patients with initial lung cancer and identify the impacts of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment on the development of SPCs. In this study, 37,954 individuals were included, of whom 2819 had SPCs. These patients were further divided into the second primary lung cancers (SPLC) and second primary extrapulmonary cancer (SPEC) groups. Among the patients with lung cancer without SPCs, those aged <65 years accounted for 53.15%. Patients aged ≥65 years accounted for 40.18% and 53.24% in the SPLC and SPEC groups, respectively. Females accounted for 50.3% of patients without SPC, 54% of the SPLC group, and 44.3% of the SPEC group. Univariate and multivariate Cox proportional hazard models showed increased hazard ratios for smoking, hypertension, and diabetes mellitus, and lower HRs for surgery, chemotherapy, radiotherapy, and TKIs. Patients undergoing surgery, chemotherapy, and radiotherapy were associated with a lower risk of SPCs. Treatment with EGFR TKIs was a significant and independent factor associated with lower incidence of SPCs. This study may encourage researchers to establish predictive models based on our results to assess the risk factors for SPCs, and therefore, early screening and intervention could be applied, and the SPCs-related mortality and relevant medical costs could be reduced. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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14 pages, 2555 KiB

Open AccessArticle

Impact of KRAS Mutation Subtypes and Co-Occurring Mutations on Response and Outcome in Advanced NSCLC Patients following First-Line Treatment

by Yingjia Sun, Ziming Li, Hong Jian, Liliang Xia and Shun Lu

J. Clin. Med. 2022, 11(14), 4003; https://doi.org/10.3390/jcm11144003 - 11 Jul 2022

Cited by 3 | Viewed by 2371

Abstract

(1) Background: The purpose was to systematically assess the impact of KRAS subtypes and co-mutations on responses of first-line treatment and outcomes by genetic classification in advanced KRAS mutant NSCLC. (2) Methods: Molecular pathology was confirmed with NGS; Kaplan–Meier analysis and Cox multivariate model were used to analyze the efficacy of first-line treatment and prognosis in KRAS subgroups. (3) Results: Advanced KRAS mutant NSCLC was confirmed among 183 patients, who received first-line therapy. The most common KRAS subtype and co-mutation were G12C (29.5%) and TP53 (59.6%). ICIs/CHE group prolonged PFS to 16.9 m, vs. (CHE)4.6 m vs. (CHE/BEV)7.0 m (p < 0.0001); mOS (ICIs/CHE)37.1 m vs. (CHE)19.8 m vs. [CHE/BEV] 20.7 m (p = 0.024). PFS benefited to different degrees after first-line ICI-based treatment in each genetic classification. KRAS G12D even benefited from OS (p = 0.045). CHE/BEV prolonged mPFS of KRAS/STK11 co-mutation (p = 0.043), but decreased mPFS in G12A subtype (p = 0.026). Multivariate analysis indicated that heavy smoking history (≥20 pack-years) (HR = 0.45, p = 0.039) predicts optimistic prognosis; PS score 1 (HR = 3.604, p = 0.002) and KRAS/SMAD4 co-mutation (HR = 4.293, p = 0.027) remained as independent predictors of shorter OS. (4) Conclusions: First-line treatment with ICI benefited KRAS-mutant-NSCLC patients and resulted in non-negative predictive value for any genetic classification. Bevacizumab should be cautiously chosen for patients with KRAS G12A subtype but is recommended for KRAS/STK11 patients. KRAS/SMAD4 is a new co-mutation genotype that displayed independent risk prognostic factors in patients with advanced KRAS-mutant NSCLC. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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13 pages, 1217 KiB

Open AccessArticle

Combined Immunotherapy with Chemotherapy versus Bevacizumab with Chemotherapy in First-Line Treatment of Driver-Gene-Negative Non-Squamous Non-Small Cell Lung Cancer: An Updated Systematic Review and Network Meta-Analysis

by Yue Chai, Xinyu Wu, Hua Bai and Jianchun Duan

J. Clin. Med. 2022, 11(6), 1655; https://doi.org/10.3390/jcm11061655 - 16 Mar 2022

Cited by 6 | Viewed by 2316

Abstract

Background: A network meta-analysis was conducted to summarize randomized control trials and updated results to evaluate the efficacy and safety profiles of existing first-line therapies for advanced non-squamous non-small cell lung cancer (NSCLC) patients without known driver gene mutations. Patients and Methods: Eligible studies were identified following a systematic search of the Cochrane Library, PubMed, Embase, Web of Science, Wanfang Data, and the China Knowledge Resource Integrated Database from January 2000 to December 2021. Results: Nineteen trials involving 8176 patients with driver-gene-negative advanced non-squamous NSCLC were included. For patients with driver-gene-negative advanced NSCLC, immunotherapy + chemotherapy (IC) significantly prolonged overall survival (OS) (hazard ratio (HR), 0.80; 95% confidence intervals (CI): 0.67–0.95) and progression-free survival (PFS) (HR, 0.68; 95% CI: 0.53–0.86) compared with bevacizumab + chemotherapy (BC), with a similar objective response rate and incidence of ≥3 treatment-related adverse events (TRAEs) (risk ratios (RR), 0.98; 95% CI: 0.79–1.21/RR, 0.89; 95% CI: 0.61–1.28; respectively) compared with BC. IC yielded a superior PFS rate (HR, 1.59; 95% CI: 1.05–2.38) compared to BC in the subgroup of patients < 65 years old. Conclusions: Currently, IC is a more efficient first-line therapy for driver-gene-negative advanced non-squamous NSCLC patients, with prolonged PFS and OS, as well as a comparatively lower risk of ≥3 TRAEs compared to BC. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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Review

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30 pages, 694 KiB

Open AccessReview

Can Liquid Biopsy Based on ctDNA/cfDNA Replace Tissue Biopsy for the Precision Treatment of EGFR-Mutated NSCLC?

by Yi-Ze Li, Sheng-Nan Kong, Yun-Peng Liu, Yue Yang and Hong-Mei Zhang

J. Clin. Med. 2023, 12(4), 1438; https://doi.org/10.3390/jcm12041438 - 10 Feb 2023

Cited by 7 | Viewed by 2337

Abstract

More and more clinical trials have explored the role of liquid biopsy in the diagnosis and treatment of EGFR-mutated NSCLC. In certain circumstances, liquid biopsy has unique advantages and offers a new way to detect therapeutic targets, analyze drug resistance mechanisms in advanced patients, and monitor MRD in patients with operable NSCLC. Although its potential cannot be ignored, more evidence is needed to support the transition from the research stage to clinical application. We reviewed the latest progress in research on the efficacy and resistance mechanisms of targeted therapy for advanced NSCLC patients with plasma ctDNA EGFR mutation and the evaluation of MRD based on ctDNA detection in perioperative and follow-up monitoring. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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24 pages, 905 KiB

Open AccessReview

KRAS Mutations in Solid Tumors: Characteristics, Current Therapeutic Strategy, and Potential Treatment Exploration

by Yunkai Yang, Huan Zhang, Shanshan Huang and Qian Chu

J. Clin. Med. 2023, 12(2), 709; https://doi.org/10.3390/jcm12020709 - 16 Jan 2023

Cited by 8 | Viewed by 4550

Abstract

Kristen rat sarcoma (KRAS) gene is one of the most common mutated oncogenes in solid tumors. Yet, KRAS inhibitors did not follow suit with the development of targeted therapy, for the structure of KRAS has been considered as being implausible to target for decades. Chemotherapy was the initial recommended therapy for KRAS-mutant cancer patients, which was then replaced by or combined with immunotherapy. KRAS G12C inhibitors became the most recent breakthrough in targeted therapy, with Sotorasib being approved by the Food and Drug Administration (FDA) based on its significant efficacy in multiple clinical studies. However, the subtypes of the KRAS mutations are complex, and the development of inhibitors targeting non-G12C subtypes is still at a relatively early stage. In addition, the monotherapy of KRAS inhibitors has accumulated possible resistance, acquiring the exploration of combination therapies or next-generation KRAS inhibitors. Thus, other non-target, conventional therapies have also been considered as being promising. Here in this review, we went through the characteristics of KRAS mutations in cancer patients, and the prognostic effect that it poses on different therapies and advanced therapeutic strategy, as well as cutting-edge research on the mechanisms of drug resistance, tumor development, and the immune microenvironment. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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25 pages, 693 KiB

Open AccessReview

Microbial Biomarkers for Lung Cancer: Current Understandings and Limitations

by Jiawen Huang and Juan Huang

J. Clin. Med. 2022, 11(24), 7298; https://doi.org/10.3390/jcm11247298 - 08 Dec 2022

Cited by 4 | Viewed by 1895

Abstract

As our “hidden organ”, microbes widely co-exist at various sites on the human body. These microbes are collectively referred to as the microbiome. A considerable number of studies have already proven that the microbiome has significant impacts on human health and disease progression, including cancers. The recent discovery of cancer-specific microbiomes renders these cancer-associated microbes as potential biomarkers and therapeutic targets. While at low biomass levels, the lung microbiome still dramatically influences the initiation, progression and treatment of lung cancers. However, research on lung cancer-associated microbiomes is emerging, and most profiling studies are performed within three years. Unfortunately, there are substantial inconsistencies across these studies. Variations in microbial diversity were observed, and different microbial biomarkers for lung cancer have been proposed. In this review, we summarized the current findings of lung cancer microbiome studies and attempt to explain the potential reasons for the dissimilarities. Other than lung microbiomes, oral and airway microbiomes are highly related to lung microbiomes and are therefore included as well. In addition, several lung cancer-associated bacterial genera have been detected by different independent studies. These bacterial genera may not be perfect biomarkers, but they still serve as promising risk factors for lung cancers and show great prognostic value. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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12 pages, 2719 KiB

Open AccessReview

Comparison of Efficacy and Safety of Brigatinib in First-Line Treatments for Patients with Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Systematic Review and Indirect Treatment Comparison

by Yongfeng Yu, Fanfan Zhu, Wenxin Zhang and Shun Lu

J. Clin. Med. 2022, 11(11), 2963; https://doi.org/10.3390/jcm11112963 - 24 May 2022

Cited by 3 | Viewed by 2615

Abstract

(1) Background: The relative efficacy and safety of brigatinib compared with other next-generation anaplastic lymphoma kinase (ALK) inhibitors remains unclear, as first-line head-to-head trials have not been conducted. (2) Methods: Electronic databases were systematically searched for eligible randomized controlled trials (RCT) from January 2010 to October 2021. Outcomes evaluated by indirect treatment comparison (ITC) included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety. (3) Results: Nine RCTs with 2484 patients assessing crizotinib, ceritinib, alectinib, brigatinib, ensartinib, and lorlatinib were included. In intent-to-treat (ITT) patients, brigatinib significantly prolonged blinded independent review committee-assessed PFS compared with crizotinib (HR: 0.48, 95% CI: 0.35 to 0.66) and ceritinib (HR: 0.38, 95% CI: 0.23, 0.60) and had a comparable PFS with other 2nd-generation ALK inhibitors. Subgroup analyses of patients with baseline brain metastases and Asian patients yielded results similar to the base case. Brigatinib significantly reduced the risk of death compared with crizotinib (HR: 0.50, 95% CI: 0.28, 0.87) after adjusting for treatment crossover in the crizotinib arm. No significant differences were observed in OS between brigatinib and other next-generation ALK inhibitors. Brigatinib had significantly superior effects in ORR and intracranial ORR compared to crizotinib. The incidence of grade ≥3 AEs was similar between brigatinib and other next-generation ALK inhibitors (except for alectinib), while brigatinib could significantly delay the time to worsening in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) global health status (GHS)/quality of life (QoL) vs. crizotinib (HR: 0.69, 95% CI: 0.49, 0.98). (4) Conclusions: Brigatinib had longer PFS compared to crizotinib and ceritinib and had comparable efficacy and safety profile with other 2nd-generation ALK inhibitors in first-line treatments for patients with ALK-positive non-small-cell lung cancer. Full article

(This article belongs to the Special Issue Target and Im-Oncology Therapeutic Approaches for Lung Cancer)

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