We treated SB28 tumor-bearing mice with vehicle, ICI, CXCL12 inhibitor (NOX-A12), or a combination of NOX-A12 with ICI...CXCL12 inhibition demonstrates therapeutic potential in facilitating anti-tumor immune response by dual mechanism, including T cell expansion and TAM reduction. The inability to deplete TAMs and improve survival in intracranial GBM underscores the need to address brain-specific mechanisms underlying TAM persistence to advance immunotherapy in GBM.

The "second chance" for FTIs is here but the successful clinical implementation of FTIs can only be achieved if the design of the new clinical trials do not repeat mistakes of the past: application of these drugs without predictive markers.

Rapid vascular recovery is a key feature preceding glioblastoma (GBM) recurrence after radiotherapy (RT). Median progression-free (PFS) and overall survival (OS) after RT + BEV + NOX-A12 were 9.1 and 19.9 months, respectively, significantly outperforming RT + NOX-A12 (p = 0.009; p = 0.021) in a post-hoc comparative analysis, with two patients exceeding 2-year OS. These findings establish proof-of-principle for dual inhibition of CXCL12 and VEGF in patients with newly-diagnosed GBM following RT.

Through analysis of representative clinical programs, including the systemic nucleolin-targeting aptamer AS1411, the microenvironment-modulating CXCL12 inhibitor NOX-A12, and the locally administered personalized platform AM003, this review highlights how delivery strategy, target context, and clinical deployment critically shape therapeutic outcomes. Recurrent translational barriers related to systemic exposure, tumor accessibility, regulatory pathways, and competition with established modalities are identified, together with lessons from both failed and emerging programs. Finally, we discuss practical strategies to improve clinical alignment, including human-relevant selection models, localized or combination therapies, and AI-assisted design, positioning aptamers for context-appropriate roles in future precision oncology.

Although most aptamer-based checkpoint inhibitors remain in preclinical stages, early phase clinical investigations (primarily with C-X-C motif chemokine ligand 12 (CXCL12)-targeting Spiegelmer NOX-A12 in combination settings, as well as earlier programs such as AS1411 targeting nucleolin) have demonstrated effective inhibition of immune checkpoint signaling, reactivation of T-cell function, and synergistic effects when combined with existing immunotherapies. Preclinical and early phase clinical investigations have demonstrated that aptamers can effectively inhibit immune checkpoint signaling, reactivate T-cell function, and potentiate synergistic effects when combined with existing immunotherapies. By critically evaluating current progress and identifying key translational challenges, this review provides strategic insights into the future development of aptamer-based immunotherapeutic platforms, ultimately guiding the advancement of more precise, cost-effective, and personalized cancer treatment modalities.

Global sensitivity analysis identified compensatory feedback, tumor proliferation rate, and PI3K-mTOR crosstalk as key determinants of tumor response. This novel QSP application exemplifies an innovative bottom-up modeling approach to support patient selection and dosing strategies for future clinical studies.

Farnesyltransferase (FTase) inhibitors (FTIs), such as tipifarnib, inhibit HRAS membrane localization and blunt RAS effector signaling, leading to an antitumor effect in HRAS-mutant FN-RMS preclinical models...Co-targeting FTase and MEK restrained tumor progression and induced terminal myogenic differentiation. These findings highlight an effective combinatorial strategy and support its preclinical translation for patients with HRAS-mutant RMS.

P1/2, N=45, Completed, Kura Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Jul 2025 | Trial primary completion date: Dec 2025 --> Jul 2025

In this study, 8 SUMO-ylation related prognostic genes were identified in BRCA, namely GPC1, CAPZA1, NUDCD1, MTDH, COX7A1, PLK3, FAM43A and CEBPD, offering fresh perspectives on the prognosis of BRCA.

However, MD simulations confirmed that both essential oil compounds exhibit binding stability comparable to that of Tipifarnib. Finally, α-humulene epoxide II and bornyl acetate from S. cumini exhibit favorable drug-like properties, high predicted safety margins, and a lack of organ-specific toxicity, underscoring their suitability for further drug development.

Our findings demonstrate that FTIs Lonafarnib and Tipifarnib impair MVM, highlighting the essential role of farnesylation in biomineralization.

The hub gene CCND1 and its targeting drug candidate Tipifarnib may contribute to PTC treatment.