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Despite advances in cancer therapy, the persistent challenge of treatment resistance and particularly multidrug resistance remains a substantial barrier to further improvements in patient outcomes. In this Review, the authors discuss preclinical and clinical advances in understanding multidrug resistance, with an emphasis on resistance to chemotherapies and targeted therapies, as well as the progress made in translating these findings into novel strategies to overcome this challenge and thus improve patient outcomes.
Cancer of unknown primary (CUP) constitutes a diagnostic quandary and has a dismal prognosis, with standard empirical chemotherapy providing limited benefit. This Review outlines diagnostic innovations that are improving tissue-of-origin prediction as well as novel treatment strategies that have shown promise for improving outcomes in patients with CUP.
This comprehensive Review describes the biological function of the mismatch repair (MMR) machinery, the genomic sequelae of defects in this machinery and the roles of hereditary or sporadic MMR deficiency in cancer predisposition and/or tumour development. The authors also discuss the clinical implications of MMR deficiency with a specific focus on diagnostic approaches, therapeutic strategies and mechanisms of resistance to immune-checkpoint inhibitors.
Despite several decades of research that has revealed roles in the development and progression of many solid tumours, clinical translation of research targeting epithelial–mesenchymal transition (EMT) has thus far been limited. In this Review, the authors provide a summary of the role of EMT in cancer development and progression in the context of this lack of clinical translation, summarize the current status of direct or indirect EMT-modulating agents in clinical development, and highlight the major barriers to the development of EMT-related clinical interventions.
The article "The molecular blueprint of targeted radionuclide therapy" from I. Primac et al. will be freely available while the November issue is featured on the journal's homepage
In this Collection, you can find the latest articles published in Nature Reviews Clinical Oncology that discuss trends in cancer incidence and mortality.
Patients with unresectable stage III non-small-cell lung cancer without EGFR or ALK mutations typically receive the PACIFIC regimen — concurrent chemoradiotherapy (cCRT) followed by consolidation with durvalumab — whereas those with EGFR-mutant disease typically receive cCRT followed by an EGFR inhibitor. Nonetheless, a subset of patients within this heterogeneous group might be able to completely avoid consolidation therapy, whereas others are unable to tolerate cCRT. In this Review, the authors describe the standard-of-care approach in this setting, followed by discussions of treatment optimization for specific subgroups, as well as important future research questions.
Extracellular vesicles (EVs), a diverse range of membrane-delimited particles, have multiple cellular functions and, when released by cancer cells, can promote tumour growth and metastatic dissemination. The authors of this Review describe advances in the development of EVs as biomarkers and cancer therapeutics, focusing on clinical translation of EVs into diagnostic and therapeutic clinical tools.
Epstein–Barr virus (EBV) infection has a key aetiological role in endemic nasopharyngeal carcinoma (NPC). The authors of this Review discuss advances in NPC screening, which leverage the detection of either plasma EBV DNA or serum antibodies targeting EBV antigens, as well as in prevention, which relies on prophylactic and therapeutic vaccines for NPC.
Patients with advanced-stage pancreatic ductal adenocarcinoma often have dismal outcomes, despite an initial response sometimes to standard-of-care chemotherapy. This treatment refractoriness partly reflects the effects of the tumour microenvironment (TME), which is highly heterogeneous but can include a dense desmoplastic stroma as well as various immune cell and cancer-associated fibroblast populations, most of which collectively promote resistance to treatment and disease progression. In this Review, the authors summarize the role of the TME in determining the outcomes of patients with pancreatic ductal adenocarcinoma, and consider novel therapeutic approaches that might promote the development of a tumour-suppressive TME.
Chimeric antigen receptor (CAR) T cell therapy is revolutionizing the treatment of haematological malignancies, but expanding applicability to solid tumours presents substantial challenges. This Review describes key strategies to optimize CAR T cell therapy for solid tumours across areas spanning from target selection to response and safety evaluation.
Some of the most consequential conflicts in oncology and medicine overall are not financial; these remain poorly defined and weakly regulated. Here we offer a policy-relevant definition and examine how reputation, ambition, ideology and institutional loyalty can shape research, guidelines, policy and hiring decisions. We argue for structural safeguards to preserve trust in medicine.
Drug-induced interstitial lung disease (DIILD) is emerging as a hidden toll of modern oncology. Diagnosis of DIILD is confounded by non-specific symptoms and the absence of validated biomarkers, leaving clinicians to navigate heterogeneous, drug-specific guidelines. Herein, we discuss this predicament and advocate a shift from reactive management towards proactive survivorship.