In recent years, metallic nanoparticles have gained increasing attention due to their prospective applications in the field of nanomedicine, with increasing research into their use in cancer therapy. In this current research, we investigated the effect of green synthesized Silver Nanoparticles (AgNPs) capped with Noctiluca scintillans algae extract. The phytochemicals present in the shell of AgNPs were identified using GC-MS. Different compounds with anticancer activity such as n-hexadecanoic acid, beta-sitosterol, stigmasterol and palmitic acid were detected among others. The effects of Algae-AgNPs synthesized were tested on MDA-MB-231 human breast cancer cells and HaCat human keratinocyte normal cells. Cell viability assay revealed a time and dose-dependent effect against breast cancer cells with a less potent effect against normal cells. The cell viability reduction is not attributed to a cytotoxic nor an antiproliferative effect of the Algae-AgNPs as attested by LDH release and BrdU incorporation. Algae-AgNPs exhibited an exceptional ability to specifically induce apoptosis in cancer cells and not normal cells. The observed effects are not attributed to the AgNPs, as demonstrated by the lack of impact of the Starch-AgNPs (used as a negative control) on cell survival and apoptosis. In addition to that, we show that Algae-AgNPs significantly reduced tumor cell migration by downregulation of matrix metalloprotease-9 levels. In vivo, the breast cancer xenograft model showed a significant reduction of tumor growth in mice treated with Algae-AgNPs. These findings highlight the promising potential of the green synthesized AgNPs as a safe targeted therapy for cancer treatment.

The 14-kilodalton human growth hormone (14 kDa hGH) N-terminal fragment derived from the proteolytic cleavage of its full-length counterpart has been shown to sustain antiangiogenic potentials. This study investigated the antitumoral and antimetastatic effects of 14 kDa hGH on B16-F10 murine melanoma cells. B16-F10 murine melanoma cells transfected with 14 kDa hGH expression vectors showed a significant reduction in cellular proliferation and migration associated with an increase in cell apoptosis in vitro. In vivo, 14 kDa hGH mitigated tumor growth and metastasis of B16-F10 cells and was associated with a significant reduction in tumor angiogenesis. Similarly, 14 kDa hGH expression reduced human brain microvascular endothelial (HBME) cell proliferation, migration, and tube formation abilities and triggered apoptosis in vitro. The antiangiogenic effects of 14 kDa hGH on HBME cells were abolished when we stably downregulated plasminogen activator inhibitor-1 (PAI-1) expression in vitro. In this study, we showed the potential anticancer role of 14 kDa hGH, its ability to inhibit primary tumor growth and metastasis establishment, and the possible involvement of PAI-1 in promoting its antiangiogenic effects. Therefore, these results suggest that the 14 kDa hGH fragment can be used as a therapeutic molecule to inhibit angiogenesis and cancer progression.

KRAS is a central oncogenic driver in multiple solid malignancies, including non-small cell lung cancer, pancreatic ductal adenocarcinoma, and colorectal cancer. Activating KRAS mutations, together with co-mutations and gene-dosage alterations, reprogram signaling pathways, cellular metabolism, and the tumor microenvironment, thereby promoting aggressive tumor behavior and therapeutic resistance. Despite recent advances, including KRAS G12C inhibitors and emerging agents targeting G12D, pan-RAS(ON), and nucleotide-free RAS, clinical responses remain limited in many KRAS-mutant contexts due to rapid and multifaceted resistance. This review aims to examine the mechanisms underlying resistance to KRAS-targeted therapies and to provide an integrated perspective on how adaptive tumor responses limit the durability of KRAS inhibition. Selective pressure from KRAS-targeted therapies drives adaptive tumor evolution through on-target alterations, rewiring of signaling networks, and non-genetic changes in cell state and the tumor microenvironment. This review synthesizes current knowledge on these resistance mechanisms and highlights emerging therapeutic strategies, including rational combination approaches, enhanced RAS pathway suppression, targeted protein degradation, and KRAS-directed immunotherapies. By integrating recent preclinical and clinical advances, this work provides a comprehensive framework for understanding resistance and improving the durability of KRAS pathway inhibition in cancer.