Osteosarcoma

P2, N=75, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

Therapeutic targeting of CXCL14 or its downstream signaling may suppress metastasis and improve outcomes for patients with osteosarcoma. These data position CXCL14 as both a biomarker of aggressive phenotypes and an actionable molecular target in pediatric bone cancer patients, warranting preclinical and clinical validation.

In conclusion, ALT is highly prevalent in osteosarcoma but is not adequately captured by known genetic correlates. Functional assays remain essential for accurate classification, and improved understanding of non-canonical ALT drivers will be critical for biomarker development and the design of targeted therapeutic strategies.

Additionally, CACNA1E is involved in therapy resistance, as evidenced by its downregulation being associated with temozolomide resistance in glioblastoma. Collectively, this evidence suggests that CACNA1E, along with other VGCC members, may serve as a potential prognostic biomarker and therapeutic target in cancer. Future research should further explore their molecular mechanisms, interactions with the tumor microenvironment, and clinical translation potential.

These findings suggest that tamoxifen enhances cisplatin-based combination therapy by promoting cell death in canine osteosarcoma at reduced drug concentrations. Combination therapies targeting estrogen-independent pathways may represent a promising strategy for improving treatment response in metastatic canine osteosarcoma and warrant further investigation.

The cases showed variable immunolabelling for S100 and alpha-smooth muscle actin, Ki-67 and p63. These cases enhance the clinicopathological spectrum of EOS in guinea pigs and highlight the importance of combining radiographic, histopathological and immunohistochemical evaluation for accurate diagnosis.

The transition from universal treatment to precision therapy in OTS requires a multi-omics approach for patient stratification. Future strategies must focus on overcoming the physical and immunological barriers of the TIME, reprogramming immunosuppressive cells, and exploiting novel targets like B7-H3 and MTAP deletion to improve outcomes for patients with advanced disease.

Overall, our study demonstrated that KIF18A is a promising therapeutic target in osteosarcoma. The novel inhibitor AM-1882 offers exceptional anti-tumor efficacy paired with a favorable, low-toxicity safety profile.

CYP26A1 expression was most frequent in giant cell tumors of bone. While also detected in a subset of other bone tumors, expression was limited or absent in most benign and malignant lesions, and entirely absent in normal bone tissue. These findings provide novel descriptive insight into CYP26A1 distribution and support further investigation into its role in retinoid-related pathways in bone tumor biology.

Co-administration of TGF-β and miR-16-1-3p markedly increased cisplatin sensitivity in wild-type U2OS cells and reduced tumor nodule volume, Ki67 expression, and metastasis in the chicken chorioallantoic membrane model. Collectively, these findings suggest that miR-16-1-3p biases TGF-β signaling output toward anti-growth responses, while attenuating pro-migratory effects through MDM2 inhibition and p53 stabilization, providing a mechanistic rationale for improving therapeutic responses in osteosarcoma.

By applying the pathway inhibitor LY294002, it was confirmed that the PI3K/Akt pathway is crucial for osteosarcoma proliferation. This study confirms that PYCR1 drives osteosarcoma cell proliferation and migration through three key mechanisms: regulating downstream genes, inhibiting ferroptosis, and activating the PI3K/Akt signaling pathway.

Subcutaneous ESOS is rare and diagnostically challenging. This case highlights the importance of imaging, histopathology, immunohistochemistry, and multidisciplinary management, particularly in resource-limited settings.