Cancer Research and Treatment

Original Articles

The Profile of Gut Microbiota in Carcinogenesis Driven by Mutant EGFR in Non–Small Cell Lung Cancer: Da-Som Kim, Eun Hye Kim, Ji Yong Kim, Dong Ha Kim, Yun Jung Choi, Jaeyi Jeong, Young Hoon Sung, Dong-Cheol Woo, Chong Jai Kim, Jae Cheol Lee, Miyong Yun, Jin-Yong Jeong, Jin Kyung Rho; Received December 9, 2024 Accepted March 2, 2025 Published online March 4, 2025; DOI: https://doi.org/10.4143/crt.2024.1177 [Epub ahead of print]

Purpose
Accumulating evidence has clarified that gut dysbiosis is involved in lung cancer development and progression. Although the relationship between tumors and gut microbiota has been extensively studied using clinical samples, no studies have examined the association between mutant epidermal growth factor receptor (EGFR)–induced lung carcinogenesis and dysbiosis in gut microbiota. Therefore, we investigated the gut microbiota profiles in stool samples from human lung-specific conditional EGFR-mutant transgenic mice during lung tumor carcinogenesis.
Materials and Methods
Stool samples were collected before tamoxifen treatment (V1) and at each time point following mutant EGFR expression in lung tissue (V2) and lung tumor appearance (V3). Fecal 16S rRNA taxonomy was analyzed to assess microbial diversity, composition, and dynamic changes at each time point.
Results
We found that microbiota richness and diversity were significantly elevated when tumors developed and grew in the lung. Phylogenetic analysis of the microbial community revealed that Lachnospiraceae, Ruminococcaceae, Porphyromonadaceae, Rhodospirillaceae, Odoribacteraceae, and Desulfovibrionaceae showed a significant increase at the V3 stage compared to the V1 stage at the family level. In contrast, Lactobacillaceae, Bacteroidaceae, Muribaculaceae, Coriobacteriaceae, and Rikenellaceae significantly decreased at the V3 stage compared to the V1 stage. Furthermore, Lactobacillus species, also known as short chain fatty acid-producing bacteria, were relatively abundant at the V1 stage but were depleted with the occurrence of lung tumors at the V3 stage.
Conclusion
Changes in gut microbiota, such as Lactobacillus species, may be a predictive factor for the emergence and progression of tumors in an animal model of lung adenocarcinoma induced by mutant EGFR.

Citations

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Gut microbiota and metabolites: emerging prospects in the treatment of non-small cell lung cancer
Jing-Mian Jiao, Chen-Guang Liu, Dan Zang, Jun Chen
Frontiers in Immunology.2025;[Epub] CrossRef
Study on the Impact of Changes in Intestinal Microbiota Structure of Lung Cancer Patients on the Efficacy of Immune Checkpoint Inhibitors
静鲁
Advances in Clinical Medicine.2025; 15(11): 744. CrossRef

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110 Download
2 Crossref

Gastrointestinal cancer

Clinical Characteristics of and Treatment Pattern for EGFR-Amplified Colorectal Cancer: Seong-Eun Kim, Hyehyun Jeong, Sun Young Kim, Jeong Eun Kim, Yong Sang Hong, Deokhoon Kim, Jihun Kim, Ji Sung Lee, Tae Won Kim; Cancer Res Treat. 2025;57(4):1104-1114. Published online January 10, 2025; DOI: https://doi.org/10.4143/crt.2024.569

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to compare clinicopathologic features and clinical outcomes of metastatic colorectal cancer (mCRC) based on epidermal growth factor receptor (EGFR) amplification status.
Materials and Methods
Patients with mCRC who underwent next-generation sequencing using a targeted 244-gene panel from 2016 to 2021 were identified and screened for EGFR copy numbers. Cases with at least five copies were reviewed for tumor purity adjustment, and those with an adjusted copy number of ≥ 6 were defined as EGFR-amplified (EGFR amp+). Their clinical characteristics were compared with those without EGFR amplification (EGFR amp–).
Results
Among 2,421 patients, 35 (1.4%) were EGFR amp+. Clinical characteristics did not significantly differ according to EGFR amplification status, but EGFR amp+ cases had fewer instances of peritoneal seeding (8.6% vs. 21.8%). Overall survival (OS) tended to be better in EGFR amp+ patients compared with EGFR amp– patients (median OS [mOS], 76 vs. 37 months; p=0.145). Among 572 patients who received anti-EGFR antibody–based chemotherapy (anti-EGFR CTx) during disease course, mOS tended to be better in 16 EGFR amp+ patients (79 months) compared with 556 EGFR amp– patients (39 months, p=0.048). Seven out of 35 EGFR amp+ patients were treated with front-line anti-EGFR CTx, and their progression-free survival did not differ from that of EGFR amp– patients treated with front-line anti-EGFR CTx (20 vs. 14 months, p=0.344).
Conclusion
This study may suggest a favorable predictive impact of EGFR amplification in patients treated with anti-EGFR CTx. However, the benefit of front-line anti-EGFR antibody treatment in this group was not notable.

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Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13): Dong-Hoe Koo, Minkyu Jung, Yeul Hong Kim, Hei-Cheul Jeung, Dae Young Zang, Woo Kyun Bae, Hyunki Kim, Hyo Song Kim, Choong-kun Lee, Woo Sun Kwon, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2024;56(4):1136-1145. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2023.1324

Abstract PDF Supplementary Material PubReader ePub

Purpose
Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods
Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results
RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion
A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

Citations

Citations to this article as recorded by

Human Epidermal Growth Factor Receptor 2 Positive Advanced Gastric or Esophagogastric Adenocarcinoma: Reflecting on the Past to Gain a New Insights
Yu Aoki, Izuma Nakayama, Kohei Shitara
Current Oncology Reports.2025; 27(1): 15. CrossRef
Pharmacotherapy for previously treated gastric cancer patients: current options and future developments
Seiya Sato, Izuma Nakayama, Kohei Shitara
Expert Review of Clinical Pharmacology.2025; 18(8): 607. CrossRef
Unraveling the future: Innovative design strategies and emerging challenges in HER2-targeted tyrosine kinase inhibitors for cancer therapy
Sixiang Zheng, Ruixian Chen, Lele Zhang, Lun Tan, Lintao Li, Fangyi Long, Ting Wang
European Journal of Medicinal Chemistry.2024; 276: 116702. CrossRef

4,416 View
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3 Web of Science
3 Crossref

Lung and Thoracic cancer

Tumor Microenvironment Modulation by Neoadjuvant Erlotinib Therapy and Its Clinical Impact on Operable EGFR-Mutant Non–Small Cell Lung Cancer: Beung-Chul Ahn, Charny Park, Moon Soo Kim, Jong Mog Lee, Jin Ho Choi, Hyae Young Kim, Geon Kook Lee, Namhee Yu, Youngjoo Lee, Ji-Youn Han; Cancer Res Treat. 2024;56(1):70-80. Published online June 21, 2023; DOI: https://doi.org/10.4143/crt.2023.482

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have greatly improved survival in EGFR-mutant (EGFRm) non–small cell lung cancer (NSCLC); however, their effects on the tumor microenvironment (TME) are unknown. We assessed the changes induced by neoadjuvant erlotinib therapy (NE) in the TME of operable EGFRm NSCLC.
Materials and Methods
This was a single-arm phase II trial for neoadjuvant/adjuvant erlotinib therapy in patients with stage II/IIIA EGFRm NSCLC (EGFR exon 19 deletion or L858R mutations). Patients received up to 2 cycles of NE (150 mg/day) for 4 weeks, followed by surgery and adjuvant erlotinib or vinorelbine plus cisplatin therapy depending on observed NE response. TME changes were assessed based on gene expression analysis and mutation profiling.
Results
A total of 26 patients were enrolled; the median age was 61, 69% were female, 88% were stage IIIA, and 62% had L858R mutation. Among 25 patients who received NE, the objective response rate was 72% (95% confidence interval [CI], 52.4 to 85.7). The median disease-free and overall survival (OS) were 17.9 (95% CI, 10.5 to 25.4) and 84.7 months (95% CI, 49.7 to 119.8), respectively. Gene set enrichment analysis in resected tissues revealed upregulation of interleukin, complement, cytokine, transforming growth factor β, and hedgehog pathways. Patients with upregulated pathogen defense, interleukins, and T-cell function pathways at baseline exhibited partial response to NE and longer OS. Patients with upregulated cell cycle pathways at baseline exhibited stable/progressive disease after NE and shorter OS.
Conclusion
NE modulated the TME in EGFRm NSCLC. Upregulation of immune-related pathways was associated with better outcomes.

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Dual Inhibition of SYK and EGFR Overcomes Chemoresistance by Inhibiting CDC6 and Blocking DNA Replication
Jayaprakash Mandal, Tiffany Nicole Jones, Juliane Marie Liberto, Stephanie Gaillard, Tian-Li Wang, Ie-Ming Shih
Cancer Research.2024; 84(22): 3881. CrossRef

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281 Download
1 Web of Science
1 Crossref

miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in Non-Small Cell Lung Cancer Cells by Targeting USP37: Mi Seong Kim, So Hui Kim, Sei Hoon Yang, Min Seuk Kim; Cancer Res Treat. 2022;54(2):445-457. Published online August 3, 2021; DOI: https://doi.org/10.4143/crt.2021.622

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