Cancer stem cells (CSCs) are a rare but highly tumorigenic subpopulation that drives tumor initiation, therapeutic resistance, metastasis, and disease recurrence. Their intrinsic resistance to conventional therapies has prompted the development of targeted strategies capable of selectively eliminating CSCs while sparing normal cells and tissues.

Surgical resection remains the cornerstone for localized gastrointestinal stromal tumors (GIST), but recurrence risk varies widely. Targeted therapy with imatinib has transformed outcomes in advanced disease and is now used in the adjuvant setting for selected patients.

Salivary gland carcinomas are highly heterogeneous malignancies that present a complex variety of histological features and distinct clinical behaviors, with salivary duct carcinoma (SDCa) as the most clinically severe and aggressive subtype. The standard of care for these patients is a combined approach of surgery followed by radiotherapy. The aggressive clinical course of SDCa is primarily driven by frequent disease recurrences and systemic spread.

Pediatric central nervous system (CNS) tumors are the most common solid malignancies in children. Advances in multimodal therapies have improved survival, resulting in a growing population of long-term survivors who often experience treatment-related morbidity affecting quality of life and functional outcomes. This underscores the importance of comprehensive survivorship care.

Fertility preservation is an increasingly important component of survivorship care for adolescent and young adult (AYA) women with central nervous system (CNS) tumors. As survival improves, attention to long-term reproductive health is increasingly needed.

Gestational trophoblastic neoplasia (GTN) comprises a group of rare malignant disorders arising from placental trophoblastic tissue. Despite the remarkable chemosensitivity of high-risk GTN, delays in diagnosis, inadequate risk stratification, or inappropriate chemotherapy regimens remain the primary determinants of adverse outcomes. Understanding the role of chemotherapy is essential to ensure optimal management, maximize cure rates, and ultimately eliminate preventable mortality associated with this disease.

T cell engagers (TCEs) are engineered immune-mobilizing molecules that recruit T cells toward tumor cells. TCEs have demonstrated clinical efficacy in hematologic malignancies and currently show therapeutic potential in solid tumors through the approvals of tebentafusp and tarlatamab in uveal melanoma and small cell lung cancer. However, implementation of TCEs in solid tumors presents distinct challenges owing to tumor intrinsic features such as lack of specific antigens, biochemical and physical barriers that hinder T cell infiltration, complex immunosuppressive microenvironments, and intrinsic or acquired resistance to TCEs.

Pediatric oncology poses distinct scientific, ethical, regulatory, and commercial challenges compared to adult oncology. Although survival rates for certain childhood malignancies have improved significantly, progress in relapsed, refractory, and rare pediatric cancers remains limited.

Rare cancers, individually uncommon but collectively significant, pose major challenges due to their heterogeneity, low incidence, and fragmented expertise. This review addresses the complexities of managing and researching rare cancers, highlighting the necessity for collaborative networks.

Biliary tract cancer (BTC) is a heterogeneous and highly lethal malignancy, with many patients presenting with locally advanced or metastatic disease unsuitable for upfront curative resection. Advances in chemotherapy, immunotherapy, and molecularly targeted therapy have created opportunities for conversion surgery in selected patients, but its role and optimal selection criteria remain uncertain.