Nature cancer最新文献

The integration of artificial intelligence (AI) into oncology promises to revolutionize cancer care. In this Review, we discuss ten AI hallmarks in precision oncology, organized into three groups: (1) cancer prevention and diagnosis, encompassing cancer screening, detection and profiling; (2) optimizing current treatments, including patient outcome prediction, treatment planning and monitoring, clinical trial design and matching, and developing response biomarkers; and (3) advancing new treatments by identifying treatment combinations, discovering cancer vulnerabilities and designing drugs. We also survey AI applications in interventional clinical trials and address key challenges to broader clinical adoption of AI: data quality and quantity, model accuracy, clinical relevance and patient benefit, proposing actionable solutions for each.

Tissue remodeling and cell plasticity in the mammary gland are activated by multilineage communications; however, the dynamic signaling promoting breast cancer remains unclear. Here, by RNA sequencing of single cells and physically interacting cells (PICs) along mammary gland development and carcinogenesis, we uncovered that neutrophils appear transiently during early development and re-emerge in physical interaction with tumor cells in advanced carcinoma. Neutrophil heterogeneity analysis characterized transcriptional states linked to age and cancer stage. Integrating ligand-receptor and PIC sequencing analyses with various functional experiments unveiled a physical and secreted protumorigenic signaling niche. This approach revealed that neutrophils are recruited by tumor-activated macrophages and physically interact with tumor cells, increasing tumor cell proliferative and invasive properties, as well as endothelial proliferation and angiogenesis. The molecular program upregulated in neutrophil-PICs correlates with lower survival in advanced breast cancer patients. Our interaction-driven perspective highlights potential molecular targets and biomarkers for breast cancer treatment.

Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We conducted a phase 2, nonrandomized, single-arm clinical trial (NCT04022343) of cabozantinib treatment for 12 weeks in 17 patients with locally advanced, biopsy-proven, nonmetastatic clear cell RCC before surgical resection. The primary end point was the objective response rate (complete and partial responses) at week 12 and secondary end points included safety, tolerability, clinical and surgical outcomes, and quality of life. Six patients (35%) experienced a partial response and 11 patients (65%) had stable disease. The most common adverse events were diarrhea (n = 12, 70.6%), anorexia, fatigue and hypertension (n = 10, 58.8%), nausea and palmar-plantar erythrodysesthesia syndrome (n = 9, 52.9%). No treatment grade 4 or 5 adverse events related to cabozantinib or surgery occurred. The 1-year disease-free survival and overall survival were 82.4% (95% CI 54.7-93.9%) and 94.1% (95% CI 65-99.1%), respectively. Cabozantinib treatment activated CD8⁺ T cells in the blood, depleted myeloid populations and induced immune niches for TCF1⁺ stem-like CD8⁺ T cells. Cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced nonmetastatic clear cell RCC.

Antigen-presenting cells phagocytose tumor cells and subsequently cross-present tumor-derived antigens. However, these processes are impeded by phagocytosis checkpoints and inefficient cytosolic transport of antigenic peptides from phagolysosomes. Here, using a microbial-inspired strategy, we engineered an antibody-toxin conjugate (ATC) that targets the 'don't eat me' signal CD47 linked to the bacterial toxin listeriolysin O from the intracellular bacterium Listeria monocytogenes via a cleavable linker (CD47-LLO). CD47-LLO promotes cancer cell phagocytosis by macrophages followed by LLO release and activation to form pores on phagolysosomal membranes that enhance antigen cross-presentation of tumor-derived peptides and activate cytosolic immune sensors. CD47-LLO treatment in vivo significantly inhibited the growth of both localized and metastatic breast and melanoma tumors and improved animal survival as a monotherapy or in combination with checkpoint blockade. Together, these results demonstrate that designing ATCs to promote immune recognition of tumor cells represents a promising therapeutic strategy for treating multiple cancers.