NRAS mutation

The cooperative GOG 281/LOGS trial showed that trametinib, an MEK inhibitor (MEKi), was significantly more effective than standard-of-care options (including chemotherapy or hormonal therapy) in increasing progression-free survival (median PFS 13.0 months vs. 7.2 months; hazard ratio 0.48, p < 0.001)...Genomic and multi-omic profiling have revealed actionable vulnerabilities and precision oncology approaches. The advent of biomarker-directed trials, molecular subtyping incorporation, and innovative computational strategies is likely to gradually ameliorate therapy selection and, thereby, finally improve long-term outcomes for patients with this complex disease.

We described the genomic landscape of KRASG12D-mutant CRC and PDAC, demonstrating that cases often have additional oncogenic alterations linked to resistance to KRAS inhibition. These alterations are also associated with a worse prognosis. Recognizing these alterations may inform new therapeutic strategies. Further studies are warranted to validate these findings in ongoing clinical trials.

The generally indolent nature of both tumors supported successful nephron-sparing surgical management. This unique case emphasizes the need for a high index of suspicion for rare tumor subtypes and a multidisciplinary approach to optimize the diagnosis and tailored treatment of complex renal masses.

Histopathological evaluation may aid risk stratification alongside KRAS status. Prognostic assessment in clinical settings should take both TNM staging and KRAS status into account.

Thus, the genomic profile of canine FTC differs significantly from that of humans, with limited reliance on RAS/RAF signaling for oncogenic progression. Conversely, RET signaling likely underlies tumorigenesis in both canine and human MTC.

In contrast, SIRT1 expression was not significantly associated with these parameters. Both SIRT1 and SIRT2 showed a statistically significant relationship with K-RAS mutations, highlighting their potential roles in the molecular pathology of colorectal cancer.

Moreover, FTY720 co-treatment resensitized G12D NRAS -mutated M14(R)701 cells to gilteritinib in vivo. Co-treatment inactivated ERK, transcriptionally downregulated SPHK1, and inactivated downstream AKT, p70S6K and BAD, with inactivation abrogated by constitutive SPHK1 expression. The clinically applicable S1PR modulators fingolimod and mocravimod resensitize NRAS -mutated FLT3-ITD AML cells to FLT3 inhibitors, supporting potential clinical efficacy of these combinations.

The ferroptosis inducer erastin also inhibits melanoma growth. Combining the ATAD2 inhibitor BAY-850 with the MEK inhibitor trametinib potently suppresses melanoma growth. Our study identifies ATAD2 as a key driver of melanoma and provides a rationale for targeting ATAD2 in conjunction with the MAPK pathway to treat melanoma.

Clinically, one patient succumbed to disease one month and another patient experienced a recurrence at 43 months, whereas the remaining patients had no evidence of disease at 3-24 months of follow-up. MLA displays unique cytomorphologic features and accurate identification of MLA on cytology should prompt confirmatory tests to exclude potential morphologic mimics and ensure appropriate diagnosis.

Subsequently, multiple hepatic metastases and pelvic dissemination developed, and conventional chemotherapy including bevacizumab was ineffective...Switching to sorafenib led to further progression, but reintroduction of LVB reduced Tg levels...The patient has survived seven years since recurrence, including six years on LVB. The tumor behaved similarly to poorly differentiated thyroid carcinoma, with Tg levels reflecting disease activity and LVB demonstrating the potential for long-term tumor control.