Cancer treatment generally involves drugs used in combinations. Most prior work has focused on identifying and understanding synergistic drug-drug interactions; however, understanding antagonistic interactions remains an important and understudied issue. To enrich for antagonism and reveal common features of these combinations, we screened all pairwise combinations of drugs characterized as activators regulated cell death. This network is strongly enriched for antagonism, particularly a form of antagonism that we call “single agent dominance”. Single agent dominance refers to antagonisms in which a two-drug combination phenocopies one of the two agents. Dominance results from differences in death onset time, with dominant drugs acting earlier than their suppressed counterparts. We explored mechanisms by which parthanatotic agents dominate apoptotic agents, finding dominance in this scenario caused by mutually exclusive and conflicting use of PARP1. Taken together, our study reveals death kinetics as a predictive feature of antagonism, due to inhibitory crosstalk between death pathways.

Due to tumor heterogeneity, most believe that effective treatments should be tailored to the features of an individual tumor or tumor subclass. It is still unclear, however, what information should be considered for optimal disease stratification, and most prior work focuses on tumor genomics. Here, we focus on the tumor microenvironment. Using a large‐scale coculture assay optimized to measure drug‐induced cell death, we identify tumor–stroma interactions that modulate drug sensitivity. Our data show that the chemo‐insensitivity typically associated with aggressive subtypes of breast cancer is not observed if these cells are grown in 2D or 3D monoculture, but is manifested when these cells are cocultured with stromal cells, such as fibroblasts. Furthermore, we find that fibroblasts influence drug responses in two distinct and divergent manners, associated with the tissue from which the fibroblasts were harvested. These divergent phenotypes occur regardless of the drug tested and result from modulation of apoptotic priming within tumor cells. Our study highlights unexpected diversity in tumor–stroma interactions, and we reveal new principles that dictate how fibroblasts alter tumor drug responses.

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Perinatal mental health issues are a global public health challenge. Worldwide, it is estimated that 10% of pregnant women, and 13% of women who have just given birth, experience a mental disorder. Yet, for many reasons – including stigma, limited access to services, patients’ lack of awareness about symptoms, and inadequate professional intervention – actual rates of clinical and subclinical perinatal mental health issues are likely higher. Studies have explored experiences such as postpartum depression, but few involve a wider‐ranging exploration of a variety of self‐reported perinatal mental health issues through personal narrative. We conducted 21 narrative interviews with women, in two Canadian provinces, about their experiences of perinatal mental health issues. Our aim was to deepen understanding of how individual and cultural narratives of motherhood and perinatal mental health can be sources of shame, guilt, and suffering, but also spaces for healing and recovery. We identified four predominant themes in women’s narrative: feeling like a failed mother; societal silencing of negative experiences of motherhood; coming to terms with a new sense of self; and finding solace in shared experiences. These findings are consistent with other studies that highlight the personal challenges associated with perinatal mental health issues, particularly the dread of facing societal norms of the ‘good mother’. We also highlight the positive potential for healing and self‐care through sharing experiences, and the power of narratives to help shape feelings of self‐worth and a new identity. This study adheres to the expectations for conducting and reporting qualitative research.