bims-meluca 2025-06-22 papers

Thorac Cancer. 2025 Jun;16(12): e70104

Effect of Cancer Cachexia on the Efficacy and Treatment Delivery of Chemotherapy in Older Patients With Advanced Small Cell Lung Cancer.

Michitoshi Yabe, Tateaki Naito, Suguru Matsuda, Meiko Morita, Motoki Sekikawa, Keita Miura, Hiroaki Kodama, Toshiya Fujisaki, Nobuaki Mamesaya, Haruki Kobayashi, Ryo Ko, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Haruyasu Murakami, Toshiaki Takahashi.

BACKGROUND: Cachexia is a syndrome in patients with cancer that reduces life quality and prognosis, characterized by severe weight loss, muscle atrophy, and anorexia. How cachexia adversely affects older patients with small cell lung cancer (SCLC) remains uncertain. This study aimed to determine the effect of cachexia on prognosis, treatment delivery, and efficacy in older patients with advanced SCLC receiving first-line platinum-based chemotherapy.
METHOD: We retrospectively analyzed older patients (≥ 70 years) with advanced SCLC treated with carboplatin and etoposide between January 2015 and June 2020 at the Shizuoka Cancer Center. Cachexia was diagnosed based on the % weight loss and body mass index. After excluding patients with no documented weight change and those who relapsed after radiotherapy, we examined the effect of cachexia on treatment delivery, progression-free survival (PFS), and overall survival (OS).
RESULTS: Cachexia was identified in 57% (28 of 49) of patients. The cachexia group experienced more frequent treatment interruptions and dose reductions than the non-cachexia group (46% vs. 10% for dose reductions, p < 0.05; 61% vs. 90% for completion of four chemotherapy courses, p < 0.05). Median PFS and OS were significantly shorter in the cachexia group compared to those in the non-cachexia group (PFS: 3.3 vs. 5.4 months; OS: 6.3 vs. 15.1 months).
CONCLUSION: Older patients with advanced SCLC and cachexia undergoing carboplatin and etoposide therapy exhibited shorter PFS and OS than those without cachexia. Treatment delivery was less effective in the cachexia group than in the non-cachexia group, suggesting that their vulnerabilities affected treatment efficacy.

Keywords: cachexia; carboplatin; etoposide; prognosis; small cell lung carcinoma

DOI: https://doi.org/10.1111/1759-7714.70104

Support Care Cancer. 2025 Jun 19. 33(7): 596

Biomarkers associated with cancer-related anorexia in lung cancer: a scoping review.

Xiaoying Sun, Yunhao Chen, Zhaohui Zhang, Chunyuan Tang, Xiaoqin Hu, Lina Wu, Qiangqiang Zhao, Shouzhen Cheng.

PURPOSE: Anorexia is a frequent and serious symptom in patients with lung cancer, often leading to malnutrition and cachexia, and negatively affecting quality of life and survival. This scoping review systematically synthesizes current evidence on biomarkers associated with cancer-related anorexia (CRA) in lung cancer, aiming to clarify biological mechanisms and inform targeted interventions.
METHODS: We performed a comprehensive literature search of studies evaluating the associations between CRA and various biomarkers in patients with lung cancer. Data were extracted and analyzed for pathway, genomic, transcriptomic, epigenetic, proteomic, metabolic, and composite biomarkers.
RESULTS: A total of 33 studies were included, identifying more than 100 biomarkers closely associated with CRA in lung cancer. These include inflammatory cytokines, energy metabolism markers, epigenetic and transcriptomic alterations, and disruptions in multiple cellular signaling pathways. Our analysis demonstrates that CRA is not the result of a single factor but reflects widespread dysregulation across metabolic, immune, and signaling networks. Some studies suggest that nutritional and anti-inflammatory interventions, such as n-3 fatty acid and antioxidant supplementation, can modulate biomarker profiles and potentially improve clinical outcomes.
CONCLUSION: CRA in lung cancer is a multifactorial syndrome involving complex interactions among inflammatory, metabolic, and signaling pathways. Multi-omics biomarker integration holds promise for early detection and individualized treatment, but larger, multi-center studies are needed to confirm clinical utility and optimize management strategies. Precision interventions based on biomarker profiles should be further explored in future research and practice.

Keywords: Biomarkers; Cancer-related anorexia; Inflammation; Lung cancer; Scoping review

DOI: https://doi.org/10.1007/s00520-025-09670-9

Cancer Metab. 2025 Jun 16. 13(1): 28

Cancer-associated fibroblasts promote drug resistance in ALK-driven lung adenocarcinoma cells by upregulating lipid biosynthesis.

Ann-Kathrin Daum, Lisa Schlicker, Marc A Schneider, Thomas Muley, Ursula Klingmüller, Almut Schulze, Michael Thomas, Petros Christopoulos, Holger Sültmann.

BACKGROUND: Targeted therapy interventions using tyrosine kinase inhibitors (TKIs) provide encouraging treatment responses in patients with ALK-rearranged lung adenocarcinomas, yet resistance occurs almost inevitably. In addition to tumor cell-intrinsic resistance mechanisms, accumulating evidence suggests that cancer-associated fibroblasts (CAFs) within the tumor microenvironment contribute to therapy resistance. This study aimed to investigate CAF-driven molecular networks that shape the therapeutic susceptibility of ALK-driven lung adenocarcinoma cells.
METHODS: Three-dimensional (3D) spheroid co-cultures comprising ALK-rearranged lung adenocarcinoma cells and CAFs were utilized to model the tumor microenvironment. Single-cell RNA sequencing was performed to uncover transcriptional differences between TKI-treated homotypic and heterotypic spheroids. Functional assays assessed the effects of CAF-conditioned medium and CAF-secreted factors on tumor cell survival, proliferation, lipid metabolism, and downstream AKT signaling. The therapeutic potential of targeting metabolic vulnerabilities was evaluated using pharmacological inhibition of lipid metabolism and by ferroptosis induction.
RESULTS: CAFs significantly diminished the apoptotic response of lung tumor cells to ALK inhibitors while simultaneously enhancing their proliferative capacity. Single-cell RNA sequencing identified lipogenesis-associated genes as a key transcriptional difference between TKI-treated homotypic and heterotypic lung tumor spheroids. CAF-conditioned medium and the CAF-secreted factors HGF and NRG1 activated AKT signaling in 3D-cultured ALK-rearranged lung tumor cells, leading to increased de novo lipogenesis and suppression of lipid peroxidation. These metabolic adaptations were critical for promoting tumor cell survival and fostering therapy resistance. Notably, both dual inhibition of ALK and the lipid-regulatory factor SREBP-1, as well as co-treatment with ferroptosis inducers such as erastin or RSL3, effectively disrupted the CAF-driven metabolic-supportive niche and restored sensitivity of resistant lung tumor spheroids to ALK inhibition.
CONCLUSIONS: This study highlights a critical role for CAFs in mediating resistance to ALK-TKIs by reprogramming lipid metabolism in ALK-rearranged lung cancer cells. It suggests that targeting these metabolic vulnerabilities, particularly through inhibition of lipid metabolism or induction of ferroptosis, could provide a novel therapeutic approach to overcome resistance and improve patient outcomes.

Keywords: 3D cell culture; Cancer-associated fibroblasts; EML4-ALK; Lipid metabolism; Lung adenocarcinoma; Therapy resistance

DOI: https://doi.org/10.1186/s40170-025-00400-7