RET (Ret Proto-Oncogene)

Given oncologic necessity, selpercatinib was reintroduced at a reduced dose (40 mg daily) without recurrence of severe transaminitis. This case highlights that selpercatinib can cause clinically significant hepatocellular DILI and underscores the diagnostic value of liver biopsy in distinguishing DILI from autoimmune hepatitis, particularly when considering safe dose modification and rechallenge.

Dynamic assessment of postoperative calcitonin kinetics enables meaningful stratification of recurrence risk among patients with medullary thyroid carcinoma and biochemical persistent disease. Incorporation of calcitonin-based growth kinetics may support more individualized postoperative surveillance strategies.

The results of Study LIBRETTO-431, an ex-US multiregional, open-label, randomized, active-controlled trial of selpercatinib versus platinum-based and pemetrexed chemotherapy with or without pembrolizumab in patients with treatment-naïve advanced rearranged during transfection fusion-positive non-small cell lung cancer, highlight the challenges of interpreting OS in trials with high crossover rates and variable postprogression therapies. Trial results demonstrated a large improvement in progression-free survival with an acceptable safety profile, but were accompanied by an immature OS analysis with a hazard ratio of 1.26, favoring the chemoimmunotherapy arm. Regardless of the position of OS in the end point hierarchy, it is critical that OS analyses include prespecified plans for data collection and analytical methods to account for the potential impact of postprogression therapies on the interpretation of study results.

P1/2, N=174, Recruiting, Tubulis GmbH | N=120 --> 174

P3, N=400, Recruiting, AstraZeneca | Not yet recruiting --> Recruiting

Early multi-kinase inhibitors such as vandetanib and cabozantinib demonstrated modest efficacy with significant toxicity, whereas the selective RET inhibitors selpercatinib and pralsetinib have achieved improved response rates and tolerability...Nonetheless, resistance, driven by secondary mutations and bypass signaling, presents a major therapeutic challenge. Ongoing development of next-generation inhibitors and combination strategies aims to overcome resistance and improve patient outcomes.

These findings reveal age- and treatment-dependent pathway dependencies beyond canonical KRAS status and support a precision oncology framework in PDAC. Conversational AI facilitated rapid, multidimensional clinical-genomic integration to uncover clinically relevant signaling substructures.

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.

Using FMI data, clinicians were able to direct patients toward clinical trials and to modify SOC clinical management for several NSCLC patients. These results demonstrate the benefit of FMI genomic profiling in identifying actionable driver mutations that would otherwise be missed by SOC methodology. The findings suggest that CGP is a promising and robust tool for improving personalized medicine in NSCLC treatment in Spain.

Children with MEN2B demonstrate a highly characteristic and complete phenotypic spectrum. However, diagnostic delay in children with sporadic MEN2B is common, often leading to lymph node metastasis at diagnosis. Enhancing awareness of its distinctive features among relevant specialists and establishing efficient multidisciplinary team-based recognition and referral pathways are crucial for achieving early genetic diagnosis, enabling timely prophylactic surgery, and ultimately improving long-term outcomes.

The use of molecular testing has increased significantly in the last 20 years, and the -adaptation of new targeted therapies has been rapid.

Patient was managed acutely with calcitonin and was started on prednisone and hydroxychloroquine. The co-occurrence of both MEN 2A and sarcoidosis is rare, adding an unexpected layer of complexity to the diagnosis. The rarity of sarcoidosis co-occurring with MEN 2A highlights the importance of considering a broad differential diagnosis, even in patients with known genetic syndromes, to ensure accurate management.