Targeted therapies in the management of advanced medullary thyroid cancer

RET Alterations in Thyroid Cancer: Molecular Mechanisms, Targeted Therapies, and Emerging Resistance.

An overview of the molecular mechanisms of RET alterations in thyroid cancer, targeted therapies, and emerging resistance to targeted treatment is provided.

Updates in systemic therapy for refractory thyroid carcinoma - targeted agents, immunotherapy, and chemotherapy.

PURPOSE OF REVIEW Systemic therapy for refractory thyroid carcinoma has moved from chemotherapy and broad multikinase inhibitors towards molecularly targeted treatment. This review summarizes recent practice-changing developments in radioiodine-refractory differentiated thyroid carcinoma, with brief updates on medullary and anaplastic thyroid carcinoma. RECENT FINDINGS Recent guidelines and clinical studies emphasize early molecular testing, and careful selection of patients for personalized systemic therapy. Lenvatinib remains the preferred first-line multikinase inhibitor for most progressive radioiodine-refractory differentiated thyroid cancers without actionable alterations, while cabozantinib is the best-supported option after lenvatinib. Selective Rearranged during transfection (RET), Neurotrophic Tropomyosin Receptor Kinase (NTRK), and Anaplastic Lymphoma Kinase (ALK) inhibitors have reshaped treatment for fusion-positive disease, and MAPK inhibition can restore radioiodine avidity in selected tumours. In anaplastic thyroid carcinoma, BRAF/MEK-directed treatment and emerging immunotherapy-targeted therapy combinations have prolonged survival and in select instances also enabled resection. SUMMARY Contemporary management of refractory thyroid carcinoma relies heavily on early molecular testing and utilizing genotype-directed targeted therapy options.

Recent advances in EGFR-targeted therapies for non-small cell lung cancer

This review discusses recent advances in EGFR-targeted therapies within the molecular landscape of classical and uncommon EGFR mutations, focusing on frontline intensification strategies in metastatic disease—specifically TKI combinations with chemotherapy or bispecific antibodies or bispecific antibodies—and emerging post-progression strategies to overcome acquired resistance mechanisms.

Current and Emerging Targeted Therapy in Advanced Gastroesophageal Adenocarcinoma

Background/Objectives: Advanced gastroesophageal adenocarcinoma (GEA) carries a poor prognosis, with median overall survival of 13–20 months despite standard chemotherapy. Since trastuzumab’s approval, biomarker-driven precision therapies have expanded rapidly. This review comprehensively summarises current and emerging targeted agents across the key molecular targets driving advanced GEA. Methods: A comprehensive literature review was conducted using PubMed, Google Scholar and Cochrane Library in accordance with PRISMA guidelines, searching English-language human studies published between February and July 2026, supplemented by updates during editing to reflect current standards. Results: HER2-directed therapy has progressed from trastuzumab through dual blockade, immunotherapy combinations, next-generation ADCs (notably trastuzumab deruxtecan) and bispecific antibodies such as zanidatamab, which has now overtaken trastuzumab in the first-line setting. CLDN18.2-targeted zolbetuximab has demonstrated survival benefit in biomarker-selected patients, with newer ADCs, BiTEs and the first approved solid-tumour CAR-T therapy (satricabtagene autoleucel) extending this target further. VEGFR2 inhibition with ramucirumab remains a cornerstone in later lines, while novel VEGF/PD-1(L1) bispecifics are under investigation. FGFR2b-targeted bemarituzumab showed early promise that weakened on phase 3 confirmation, and MET/EGFR-directed agents, including savolitinib and amivantamab, require stringent biomarker selection to demonstrate benefit amid tumour heterogeneity. Conclusions: Novel targeted agents, particularly to HER2 and CLDN18.2, have demonstrated survival benefit despite ongoing challenges. Other lines are more investigational.

Targeted therapies in advanced non-small-cell lung cancer: new biomarkers and treatment strategies.

Precision oncology has changed the management of advanced non-small-cell lung cancer (NSCLC). Biomarker-matched therapies now improve outcomes in an increasing number of molecularly defined subgroups. In this second paper in a Series on therapeutics in lung cancer, we summarise recent advances in NSCLC with established alterations, including EGFR, ALK, ROS1, KRAS, BRAF, RET, HER2, MET, and NTRK, and discuss emerging targets, such as NRG1 fusions, MTAP loss, and SMARCA4 deficiency. Newer generations of tyrosine kinase inhibitors, the introduction of bispecific antibodies, and antibody-drug conjugates have improved response durability, intracranial disease control, and in some settings, overall survival. However, durable benefit can remain limited by acquired resistance, tumour heterogeneity, lineage plasticity, and off-target escape, supporting repeat tissue biopsy and circulating-tumour DNA profiling to guide subsequent treatment. With several options available such as monotherapy and combination approaches, individualised treatment selection is becoming increasingly complex. We discuss these choices, including the management of CNS disease and oligoprogression, and long-term tolerability. As drug development extends beyond canonical drivers to rarer alterations and adverse co-mutations, the range of targetable disease is increasing. Further progress will depend on more effective and adaptive treatment strategies together with equitable access to comprehensive molecular profiling, timely biomarker testing, and next-generation targeted therapies.

Neoadjuvant therapy in thyroid cancer: an emerging approach