RET mutation

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.

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.

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.

Herein, we present a rare case of MTC that caused hypercalcemia via PTHrP production. Although HHM is uncommon in thyroid cancer, the condition can cause severe hypercalcemia requiring prompt diagnosis and treatment. HHM should be considered in patients with thyroid cancer with hypercalcemia, and PTHrP measurement may aid in the diagnosis.

Upon re-evaluation one year later, imaging revealed recurrent paratracheal, pulmonary, hepatic, and possible adrenal metastases, prompting re-initiation of selpercatinib at a reduced dose, which she tolerated and continues to this day with surveillance of symptoms, serial electrocardiograms, laboratory work, and imaging. This case illustrates the aggressive course of RET M918T-mutated MEN2B and underscores the importance of early genetic diagnosis, vigilant surveillance, and continuity of selective RET inhibitor therapy to optimize disease control.

In addition, 9 exhibited remarkable antitumor activity at a dose of 10 mg/kg/day, indicating that it completely hindered the growth of tumors induced by BAF3-KIF3B-RET-WT xenografts. In summary, 9 can be demonstrated to act as a potential RET inhibitor, as well as a treatment for RET-related cancers.

P2/3, N=230, Not yet recruiting, Swiss Cancer Institute | Initiation date: Dec 2025 --> Jul 2026

P2, N=60, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting

However, QTc prolongation occurred in both of our patients, suggesting that it may represent a clinically relevant concern in selected individuals. Appropriate dose adjustment and careful monitoring may facilitate continued treatment in selected patients.

These findings identify age- and treatment-specific signaling dependencies extending beyond canonical KRAS alterations and reinforce a precision oncology framework in PDAC. Conversational AI enabled rapid, multidimensional integration of clinical and genomic data, facilitating the identification of clinically meaningful pathway architectures.