Nature Reviews Clinical Oncology最新文献

Chimeric proteins resulting from fusions involving NRG1, which encodes a growth factor from the EGF family, promote HER2–HER3 heterodimerization and subsequent oncogenic activation of cell proliferation. These fusions occur in <1% of solid tumours including non-small-cell lung cancer (NSCLC) and pancreatic adenocarcinoma (PDAC). Now, data from the phase II eNRGy trial demonstrate that the HER2 × HER3 bispecific antibody zenocutuzumab is efficacious and safe in patients with advanced-stage NRG1 fusion-positive solid tumours.

The primary efficacy population comprised 158 patients with one of ten solid tumour types, primarily NSCLC (n = 94) and PDAC (n = 36). Most patients had received previous systemic therapy for metastatic disease, including 77% and 92% of those with NSCLC and PDAC, respectively. The primary end point was objective response rate (ORR).

CD19-targeted chimeric antigen receptor (CAR) T cells have provided a breakthrough in the treatment of patients with relapsed and/or refractory large B cell lymphoma (LBCL). Currently, three CD19-targeted CAR T cell products are approved by the FDA and various other regulators for the treatment of patients with LBCL: axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel. Response rates following infusion of these CD19-targeted CAR T cells have been promising; however, approximately half of treated patients show relapse within 2 years. Furthermore, receiving these agents can be associated with serious toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. In this Review, we summarize the factors associated with the efficacy, including response and survival outcomes, and toxicity of CD19-targeted CAR T cells in pivotal clinical trials and large real-world datasets describing the outcomes of patients with LBCL who received treatment with these products.

The past decade has seen the introduction of artificial intelligence (AI)-based approaches aimed at optimizing several workflows across many medical specialties. In clinical oncology, the most promising applications include those involving image analysis, such as digital pathology. In this Perspective, we provide a comprehensive examination of the developments in AI in digital pathology between 2019 and 2024. We evaluate the current landscape from the lens of technological innovations, regulatory trends, deployment and implementation, reimbursement and commercial implications. We assess the technological advances that have driven improvements in AI, enabling more robust and scalable solutions for digital pathology. We also examine regulatory developments, in particular those affecting in-house devices and laboratory-developed tests, which are shaping the landscape of AI-based tools in digital pathology. Finally, we discuss the role of reimbursement frameworks and commercial investment in the clinical adoption of AI-based technologies. In this Perspective, we highlight both the progress and challenges in AI-driven digital pathology over the past 5 years, outlining the path forward for its adoption into routine practice in clinical oncology.

Patients with HER2-negative advanced-stage gastric or gastro-oesophageal junction (G/GEJ) adenocarcinomas typically receive chemotherapy with or without an anti-PD-1 antibody as first-line treatment. Now, data from the phase III COMPASSION-15 trial show that combination of the PD-1 × CTLA4 bispecific antibody cadonilimab plus chemotherapy is also efficacious in this setting.

In this trial, conduced in China, 610 patients were randomly allocated (1:1) to receive chemotherapy (oxaliplatin–capecitabine) plus either cadonilimab or placebo. Overall survival (OS) was the primary end point.

Patients with resectable mid–low rectal cancers often undergo total mesorectal excision (TME) surgery. Over the past decade, considerable research interest has been focused on minimally invasive TME procedures that might offer improved perioperative outcomes and preservation of sphincter function, including laparoscopic and transanal approaches. Despite some evidence of an increased risk of local recurrence with the transanal approach, only limited data on long-term outcomes are available. Now, data from the phase III TaLaR trial indicate similar 3-year survival outcomes among patients undergoing these procedures.

A total of 1,115 patients with stage I–III mid–low rectal cancer (located within 10 cm of the rectal verge) requiring TME surgery were randomly assigned (1:1) to undergo transanal or laparoscopic TME across 16 centres in China. Noninferior 3-year disease-free survival (DFS) was the primary end point.

In the past two decades, treatment for non-small-cell lung cancers (NSCLCs) and head and neck squamous cell carcinoma (HNSCC) has advanced considerably, owing largely to the characterization of distinct oncological subtypes, the development of targeted therapies for each subtype and the advent of immunotherapy. Data emerging over the past two decades suggest that NUT carcinoma, a highly aggressive malignancy driven by a NUT fusion oncoprotein and arising in the lungs, head and neck, and rarely in other sites, is a squamous cell carcinoma (SCC) based on transcriptional, histopathological, cell-of-origin and molecular characteristics. NUT carcinoma has an estimated incidence of 1,400 cases per year in the United States, surpassing that of some rare NSCLC and HNSCC subtypes. However, NUT carcinoma is currently not recognized as an SCC of the lungs or head and neck. The orphan classification of NUT carcinoma as a distinct entity leads to a lack of awareness of this malignancy among oncologists and surgeons, despite early diagnosis being crucial for this cancer type with a median survival of only ~6.5 months. Consequently, NUT carcinoma is underdiagnosed and often misdiagnosed, resulting in limited research and progress in developing effective treatments in one of the most aggressive forms of lung and head and neck cancer. With a growing number of targeted agents that can potentially be used to treat NUT carcinoma, improved recognition through reclassification and inclusion of NUT carcinoma as a squamous NSCLC or an HNSCC when arising in these locations will accelerate the development of effective therapies for this disease. Thus, in the Perspective, we propose such a reclassification of NUT carcinoma as an SCC and discuss the supporting evidence.