HRAS mutation

This case highlights the consideration of functioning metastases in persistent post-thyroidectomy thyrotoxicosis and demonstrates the potential effectiveness of RAI therapy when metastatic lesions retain iodine avidity. Oncogenic mutations such as HRAS may contribute to the pathophysiology of hormone-producing metastases and provide insights into tumor differentiation and therapeutic responsiveness.

Despite vandetanib treatment, the disease progressed and the patient expired. This case highlights a rare presentation of a metastatic neoplasm highly suggestive of RET wild-type MTC with peritoneal involvement, despite the absence of an identifiable primary lesion.

P1, N=300, Recruiting, Kura Oncology, Inc. | N=66 --> 300

The frequent RAS mutations and overlapping transcriptomic profiles raise important diagnostic considerations and highlight the need for integrated molecular analyses to differentiate these entities. The EMCs displayed a recurrent HRAS mutation, also observed in other head and neck tumors, and were partially clustered with the cases of BCA, suggesting potential biological similarities.

P2, N=40, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Jan 2026

P1/2, N=5, Completed, National Cancer Institute (NCI) | N=70 --> 5 | Recruiting --> Completed

We also found that karyotype has limited utility in the setting of NB. Based on this data, we developed an institutional workflow for NB, including MYCN FISH, CMA, and NGS.

While KRAS was long considered undruggable, the development of mutant-specific inhibitors, including covalent inhibitors targeting KRASG12C (such as Sotorasib and Adagrasib) and non-covalent inhibitors targeting KRASG12D (such as Mirati's MRTX1133), has shown promise. In cellular models of KRAS-mutated NSCLC and PDAC, this nanoplatform achieved comparable or superior therapeutic outcomes with respect to the individual drugs. This study provides a compelling proof-of-concept for the in vitro delivery of KRASG12C mutant-specific inhibitors and degraders to human tumors through a tumor microenvironment-activated nanomedicine approach and lays the groundwork for future studies in physiologically relevant models to assess TME-specific activation and tumor selectivity.

Future studies should investigate whether similar genetic alterations in morphologically normal urothelium occur in other urothelial tumors. This could refine understanding of early tumorigenesis and guide improved detection and risk assessment.

Co-occurring genetic alterations with RAS mutations markedly increased the risk of malignancy compared with isolated RAS mutations (Fisher's exact test, two-tailed p = 0.0026) and were associated with more aggressive tumor phenotypes, whereas isolated RAS mutations were more common in indolent neoplasms. Comprehensive molecular profiling is essential for accurate risk stratification and management of indeterminate thyroid nodules.

CD5, CD117 and Glut1 are diffusely expressed in MNC, but not in MNT. The genetic alterations in MNC are more diverse than those of MNT, but MNC lacks the characteristic GTF2I mutation of MNT.

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027