The Society of Surgical Oncology’s (SSO) website, Surgonc.org, received a 2019 W3 Award in the category, General Websites – Associations. The W³ Awards celebrates digital

Chemotherapy usually works by inducing DNA damage that leads to cell death. However, rather than dying after chemotherapy, some tumour cells enter an inactive state, termed senescence, in which they are alive but have permanently stopped dividing1. Although senescence in normal cells drives ageing and tissue degeneration2, cancer-therapy-induced senescence is associated with positive clinical outcomes3. Understanding the factors that drive the senescence of tumour cells might thus aid the development of new anticancer treatments. Writing in Cell, Hsu et al.4 shed light on a previously unknown aspect of how chemotherapy-induced entry into senescence is controlled.

In the United States, colorectal cancer deaths in 2018 were estimated at 50,6301. Currently, regional and distant stages represent 35% and 21% of the total colorectal cancer cases, and five-year survival rates are 71.1% and 13.8%, respectively, emphasizing the impact of metastasis on survival1. Three categories of drug therapies are used for metastatic colorectal cancer treatment: chemotherapy, targeted therapy, and immunotherapy. Chemotherapy drugs target highly proliferating cells while approved targeted therapies aim to inhibit proteins in the angiogenesis pathway, such as vascular endothelial growth factor (VEGF)2. More recently, VEGF has been shown, in addition to its proangiogenic effects, to hinder immune function in the tumor microenvironment by impacting infiltration of T cells3,4.

This validation study assesses the clinical validity of molecular relapse detection with circulating tumor DNA analysis in early-stage breast cancer.

Analysis of more than 17,000 tumours suggests that the contribution of germline and somatic mutations in the BRCA1 and BRCA2 genes to oncogenesis depends on tumour lineage.

This post hoc analysis investigates the prognostic and predictive role of primary tumor location according to BRAF, RAS, and microsatellite instability status in patients with colon cancer.

Plasma genotyping identifies potentially actionable mutations at variable mutant allele frequencies, often admixed with multiple subclonal variants, highlighting the need for their clinical and functional validation. We prospectively monitored plasma genotypes in 143 women with endocrine-resistant metastatic breast cancer (MBC), identifying multiple novel mutations including HER2 mutations (8.4%), albeit at different frequencies highlighting clinical heterogeneity. To evaluate functional significance, we established ex vivo culture from circulating tumor cells (CTCs) from a patient with HER2-mutant MBC, which revealed resistance to multiple targeted therapies including endocrine and CDK 4/6 inhibitors, but high sensitivity to neratinib (IC50: 0.018 μM). Immunoblotting analysis of the HER2-mutant CTC culture line revealed high levels of HER2 expression at baseline were suppressed by neratinib, which also abrogated downstream signaling, highlighting oncogenic dependency with HER2 mutation. Furthermore, treatment of an index patient with HER2-mutant MBC with the irreversible HER2 inhibitor neratinib resulted in significant clinical response, with complete molecular resolution of two distinct clonal HER2 mutations, with persistence of other passenger subclones, confirming HER2 alteration as a driver mutation. Thus, driver HER2 mutant alleles that emerge during blood-based monitoring of endocrine-resistant MBC confer novel therapeutic vulnerability, and ex vivo expansion of viable CTCs from the blood circulation may broadly complement plasma-based mutational analysis in MBC.

Circulating tumor DNA analysis: clinical implications for colorectal cancer patients. A systematic review. Circulating Tumor DNA Analysis: Clinical Implications for Colorectal Cancer Patients. A Systematic

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