The confluence of new technologies with artificial intelligence (AI) and machine learning (ML) analytical techniques is rapidly advancing the field of precision oncology, promising to improve diagnostic approaches and therapeutic strategies for patients with cancer. By analyzing multi-dimensional, multiomic, spatial pathology, and radiomic data, these technologies enable a deeper understanding of the intricate molecular pathways, aiding in the identification of critical nodes within the tumor’s biology to optimize treatment selection. The applications of AI/ML in precision oncology are extensive and include the generation of synthetic data, e.g., digital twins, in order to provide the necessary information to design or expedite the conduct of clinical trials. Currently, many operational and technical challenges exist related to data technology, engineering, and storage; algorithm development and structures; quality and quantity of the data and the analytical pipeline; data sharing and generalizability; and the incorporation of these technologies into the current clinical workflow and reimbursement models.

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified. METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II–induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis. RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of SMCs from a primary contractile phenotype to proliferative, extracellular matrix–producing, and inflammatory phenotypes. Lineage tracing showed the complete transformation of SMCs to fibroblasts and macrophages. Single-cell sequencing assay for transposase-accessible chromatin analysis indicated that these phenotypic alterations were controlled by chromatin remodeling marked by the reduced chromatin accessibility of contractile genes and the induced chromatin accessibility of genes involved in proliferation, extracellular matrix, and inflammation. IRF3 (interferon regulatory factor 3), a proinflammatory transcription factor activated by cytosolic DNA, was identified as a key driver of the transition of aortic SMCs from a contractile phenotype to an inflammatory phenotype. In cultured SMCs, cytosolic DNA signaled through its sensor STING (stimulator of interferon genes)-TBK1 (tank-binding kinase 1) to activate IRF3, which bound and recruited EZH2 (enhancer of zeste homolog 2) to contractile genes to induce repressive H3K27me3 modification and gene suppression. In contrast, double-stranded DNA–STING-IRF3 signaling induced inflammatory gene expression in SMCs. In Sting ^–/– mice, the aortic stress–induced transition of SMCs into an inflammatory phenotype was prevented, and SMC populations were preserved. Finally, profound SMC phenotypic alterations toward diverse directions were detected in human ascending thoracic AAD tissues. CONCLUSIONS: Our study reveals the dynamic epigenetic induction of SMC phenotypic alterations in AAD. DNA damage and cytosolic leakage drive SMCs from a contractile phenotype to an inflammatory phenotype.

Coronavirus outbreak has affected thousands of people in at least 186 countries which has affected the cancer care delivery system apart from affecting the overall health system. Cancer patients are more susceptible to coronavirus infection than individuals without cancer as they are in an immunosuppressive state because of the malignancy and anticancer treatment. Oncologists should be more attentive to detect coronavirus infection early, as any type of advanced cancer is at much higher risk for unfavorable outcomes. Oncology communities must ensure that cancer patients should spend more time at home and less time out in the community. Oncologists and other health care professionals involved in cancer care have a critical opportunity to communicate to their patients to pass on right information regarding practice modifications in view of COVID-19 outbreaks. Countries must isolate, test, treat and trace to control the coronavirus pandemic. There is a paucity of information on novel coronavirus infection and its impact on cancer patients and cancer care providers. To date, there is no scientific guideline regarding management of cancer patients in a background of coronavirus outbreak.