AXL-L

Whole-exome sequencing indicates that APOEhigh expression in patients with melanoma is associated with resistance to ferroptosis, regardless of APOE germline status. In aggregate, we found a ferroptosis-resistance mechanism between melanoma cell states relying on secreted ApoE and APOEhigh expression as a potential biomarker for poor ferroptosis response in melanoma.

Remarkably, Nap-IR can synergistically enhance the anticancer effect of cisplatin against HO8910 ovarian tumors...Remarkably, Nap-IR can synergistically enhance the anticancer effect of cisplatin against HO8910 ovarian tumors. We anticipate that our Nap-IR can be applied in clinical ovarian cancer therapy in the near future.

Notably, we found the anti-AXL CAR-NK cells could inhibit the BRAFi-resistant melanoma growth and metastasis in vivo preclinical mouse models. Conclusions Our findings propose that Anti-AXL CAR-NK cell immunotherapy is a promising approach to target BRAF inhibitor drug-resistant and metastatic melanoma.

In a population of Hispanic patients with EGFR mutations, the presence of TP53 commutations negatively impacts response, PFS, and OS to Osimertinib. The biology of EGFR/TP53 tumors appears to be more aggressive, especially in the presence of the L858R variant. Prospective studies are required to characterize this population, considering the use of additional therapies to Osimertinib in patients with EGFR/TP53 with high TMB and additional genomic alterations.

Osimertinib is a third-generation EGFR-Tyrosine Kinase inhibitor (TKI) that has activity against EGFR exon 19, exon 21, and T790M mutations...AXL and STAT inhibition are associated with induced DNA damage and impaired DNA repair. From these data, we infer that DNA damage repair pathways could be involved in TKI resistance and NERx329 could be a promising drug candidate for combination targeted therapy.

In addition, plasma membrane Axl concentrations differ by 100 times between chemosensitive (OVCAR3) and chemoresistant (OVCAR8) cells and by 10 times between chemoresistant cell lines (OVCAR5 vs. OVCAR8). These systematic findings can guide ovarian cancer model selection for drug screening.

The Results show that high levels of AXL expression in tumors impact clinical predictions when using osimertinib to treat EGFR-mutated NSCLC patients.

We find that melanoma cell lines characterized as proliferative (high MITF low AXL), transform into an invasive (low MITF, high AXL) cell state after vemurafenib resistance, indicating novel feedback loops and advanced compensatory regulation mechanisms between the master regulators, receptors, and ligands involved in vemurafenib-induced resistance. Together, our data disclose fine-tuned mechanisms involved in RTK-facilitated vemurafenib resistance that will be challenging to overcome by using single drug targeting strategies against melanoma.

The results show that high AXL expression levels in tumors impact clinical predictions when using osimertinib to treat EGFR-mutated NSCLC patients. Trial Registration: UMIN000043942.