ARID1A mutational status in non-small cell lung cancer: from molecular pathology to clinical implications with a focus on the relationships with EGFR DOI Creative Commons
Claudia Di Lecce,

Serena Eccher,

Michele Simbolo

et al.

Lung Cancer, Journal Year: 2025, Volume and Issue: 205, P. 108594 - 108594

Published: June 1, 2025

Lung cancer is the most frequently diagnosed malignancy worldwide and remains leading cause of cancer-related mortality. Non-small-cell lung (NSCLC) prevalent type cancer, with epidermal growth factor receptor (EGFR) gene mutations being among reported. ARID1A (AT-Rich Interactive Domain 1A), a key component switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, has emerged as tumor suppressor in multiple cancers mutated approximately 8 % cancers, primarily loss-of-function (LOF) alteration, which allows to be considered potential molecular marker, predictive poor NSCLC prognosis. Co-occurrence LOF EGFR alterations presents complex biological therapeutic challenges. negatively affect efficacy tyrosine kinase inhibitors (EGFR-TKIs) via several mechanisms, including aberrant activation phosphoinositide 3-kinase/serine-threonine (PI3K/AKT) signaling pathway. This leads decreased apoptosis, increased angiogenesis, enhanced proliferation, greater metastatic potential. On other hand, have promising biomarkers for favorable responses immune checkpoint (ICIs). The underlying mechanisms include modulation epithelial-to-mesenchymal transition (EMT), microenvironment (TIME), impaired mismatch repair (MMR) function, mutation burden (TMB), neoantigen presentation, upregulation programmed death ligand 1 (PD-L1) I interferon (IFN-I) expression. These findings highlight dual role prognostic biomarkers, underscoring need further investigation into their implications.

Language: Английский

Mapping molecular landscapes in triple-negative breast cancer: insights from spatial transcriptomics DOI
Fares Saeed H. Al-Mansour, Hassan H. Almasoudi, Ali Albarrati

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

Language: Английский

Citations

0
Oncogenic Signalling Pathways in Cancer Immunotherapy: Leader or Follower in This Delicate Dance? DOI Open Access
Douglas Cartwright, Andrew Kidd, Sonam Ansel

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4393 - 4393

Published: May 6, 2025

Immune checkpoint inhibitors have become a mainstay of treatment in many solid organ malignancies. Alongside this has been the rapid development identification and targeting oncogenic drivers. The presence alterations drivers not only predicts response to target therapy but can modulate immune microenvironment influence immunotherapy. Combining with targeted agents is an attractive therapeutic option overlapping toxicity profiles may limit clinical use some combinations. In addition, there growing evidence shared resistance mechanisms that alter immunotherapy when it used after therapy. Understanding complex interaction between drivers, vital for selecting right treatment, at time patient. review, we summarise preclinical four common on inhibitor response, combination therapies, mechanisms. We highlight need more randomised trials investigating both sequential

Language: Английский

Citations

0
Role of TGFβ-activated cancer-associated fibroblasts in the resistance to checkpoint blockade immunotherapy DOI Creative Commons
Weibin Hou

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: May 21, 2025

Immune checkpoint blockers (ICBs) have revolutionized cancer treatment by enabling durable responses. However, most patients showed resistance and limited efficacy. Elucidating mechanisms of is imperative to extend the clinical utility ICBs. Emerging evidence highlights cancer-associated fibroblasts (CAFs), particularly TGFβ-activated myofibroblastic CAFs, as key orchestrators immunosuppressive TMEs ICBs resistance. These CAFs drive T-cell exclusion preventing intratumoral T cells from engaging cells. This review explores role TGFβ signaling in driving immune evasion therapy While targeting or directly has shown inconsistent results, downstream molecules including induced (βig-h3), endocytic receptor 180 (Endo180), leucine-rich repeat containing 15 (LRRC15), NADPH oxidase 4 (NOX4), emerge promising therapeutic targets counteract restore immunotherapy sensitivity. Advancing research on CAF heterogeneity pro-tumorigenic subsets may uncover innovative strategies expand benefits.

Language: Английский

Citations

0
ARID1A mutational status in non-small cell lung cancer: from molecular pathology to clinical implications with a focus on the relationships with EGFR DOI Creative Commons
Claudia Di Lecce,

Serena Eccher,

Michele Simbolo

et al.

Lung Cancer, Journal Year: 2025, Volume and Issue: 205, P. 108594 - 108594

Published: June 1, 2025

Lung cancer is the most frequently diagnosed malignancy worldwide and remains leading cause of cancer-related mortality. Non-small-cell lung (NSCLC) prevalent type cancer, with epidermal growth factor receptor (EGFR) gene mutations being among reported. ARID1A (AT-Rich Interactive Domain 1A), a key component switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, has emerged as tumor suppressor in multiple cancers mutated approximately 8 % cancers, primarily loss-of-function (LOF) alteration, which allows to be considered potential molecular marker, predictive poor NSCLC prognosis. Co-occurrence LOF EGFR alterations presents complex biological therapeutic challenges. negatively affect efficacy tyrosine kinase inhibitors (EGFR-TKIs) via several mechanisms, including aberrant activation phosphoinositide 3-kinase/serine-threonine (PI3K/AKT) signaling pathway. This leads decreased apoptosis, increased angiogenesis, enhanced proliferation, greater metastatic potential. On other hand, have promising biomarkers for favorable responses immune checkpoint (ICIs). The underlying mechanisms include modulation epithelial-to-mesenchymal transition (EMT), microenvironment (TIME), impaired mismatch repair (MMR) function, mutation burden (TMB), neoantigen presentation, upregulation programmed death ligand 1 (PD-L1) I interferon (IFN-I) expression. These findings highlight dual role prognostic biomarkers, underscoring need further investigation into their implications.

Language: Английский

Citations

0