AXL (AXL Receptor Tyrosine Kinase)

By blocking the mechanisms that lead to angiogenesis and tumor growth, first-line systemic treatments, such the multi-tyrosine kinase inhibitors (TKIs) lenvatinib and sorafenib, have shown moderate improvements in survival. However, their long-term efficacy is significantly reduced by intrinsic and acquired resistance, which is why second-line medications like regorafenib, cabozantinib, and ramucirumab are being studied. When combined with anti-VEGF treatments, parallel developments in immunotherapy, in particular immune checkpoint inhibitors (ICIs) such as atezolizumab and nivolumab, have shown promising outcomes...In the end, the review promotes the combination of dynamic molecular profiling and biomarker-driven precision medicine to enhance patient stratification, improve treatment decision-making, and provide long-lasting clinical effects. A strategic foundation for future advancements and individualized treatment of hepatocellular carcinoma is provided by this comprehensive synthesis.

Key molecular mechanisms underlying these synergistic effects include modulation of reactive oxygen species production, PARP activation, HR pathway regulation, cell cycle control, and induction of autophagy and apoptosis. Nevertheless, challenges including drug resistance, toxicity, and heterogeneous clinical responses highlight the need for biomarker-driven patient selection, optimized dosing schedules, and a deeper understanding of tumor-specific signaling crosstalk.

High baseline expression of BRAFi/MEKi resistance-associated proteins (e.g., AXL, YAP, HSP70, and phospho-AKT) was predictive of the response to BRAFi/MEKi + dasatinib combination therapy. These findings suggest that adding dasatinib may help overcome resistance and restore anti-tumor activity in patients with BRAFi/MEKi-refractory cutaneous melanoma.

In MKN-45 cells, merestinib increased the expression of pro-apoptotic proteins and decreased phosphorylation of c-Met, EGFR, IGF-1R, ERK, and AKT. These results indicate that combining merestinib with nab-paclitaxel may represent a promising therapeutic strategy to improve outcomes for patients with GAC.

Conversely, SOX4 also acts as an oncogene, and TFF3 as a potential tumor suppressor, both linked to OS. Targeting CCND1 and its OS-mediated regulatory pathways offers a promising therapeutic strategy for PTC.CCND1, oxidative stress, papillary thyroid carcinoma, single-cell RNA sequencing, SOX4, TFF3.

We established an efferocytosis-related prognostic signature and elucidated its underlying mechanism wherein MAGEA11 promoted immunosuppression via a Gas6-MERTK/AXL-dependent efferocytosis circuit. This integrated study positions efferocytosis as a key driver of the OS microenvironment and a promising target for clinical intervention.

Inhibition of AXL and/or Arf1 disrupted Golgi organization, tubulin acetylation and cell-surface glycosylation. Together, our findings reveal a mechanoresponsive AXL-Arf1-Golgi signaling axis that integrates matrix stiffness sensing with Golgi organization and function in breast cancer cells.

Acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), particularly osimertinib, remains a major therapeutic challenge in EGFR-mutant lung cancer...These effects were enhanced when combined with brigatinib, a clinically approved multi-kinase inhibitor with activity against mutant EGFR...Collectively, these findings suggest that magnolol exerts multitargeted effects involving inhibition of mutant EGFR, suppression of the AXL-cMyc signaling axis, and disruption of DNA repair, thereby sensitizing resistant tumors to EGFR-TKIs. Magnolol may represent a promising adjuvant strategy for overcoming acquired resistance in EGFR-mutant lung cancer.

The strong association of KRAS mutations with high PD-L1 expression, irrespective of smoking history, highlights the interplay between genetic and immunological pathways in NSCLC. These findings support the routine implementation of broad molecular testing to guide precision oncology approaches in both adenocarcinoma and squamous cell carcinoma patients.

The multiple mechanisms leading to the exclusion of relevant immune cells needed for an anti-cancer response and mechanisms leading to active immune suppression are part of complex cell-cell crosstalk. This study provides a deeper insight into the immune exhausted phenotype in CCA.

Our findings indicate that hMENA overexpression in CAFs defines a myofibroblast-like subset predominantly driven by TGF-β signaling, which sustains TGF-β1-mediated crosstalk between cancer cells and CAFs and impairs T-cell functionality. In NSCLC tissues, hMENAhigh CAFs associate with TGF-β and regulatory T-cell signatures and correlate with poor patient prognosis and resistance to immune checkpoint therapies, supporting their role as key contributors to an immunosuppressive, ICT-refractory tumor microenvironment.