Policy Implications for Protecting Health from the Hazards of Fire Smoke. A Panel Discussion Report from the Workshop Landscape Fire Smoke: Protecting Health in an Era of Escalating Fire Risk.

Globally, and nationally in Australia, bushfires are expected to increase in frequency and intensity due to climate change. To date, protection of human health from fire smoke has largely relied on individual-level actions. Recent bushfires experienced during the Australian summer of 2019-2020 occurred over a prolonged period and encompassed far larger geographical areas than previously experienced, resulting in extreme levels of smoke for extended periods of time. This particular bushfire season resulted in highly challenging conditions, where many people were unable to protect themselves from smoke exposures. The Centre for Air pollution, energy and health Research (CAR), an Australian research centre, hosted a two-day symposium, Landscape Fire Smoke: Protecting health in an era of escalating fire risk, on 8 and 9 October 2020. One component of the symposium was a dedicated panel discussion where invited experts were asked to examine alternative policy settings for protecting health from fire smoke hazards with specific reference to interventions to minimise exposure, protection of outdoor workers, and current systems for communicating health risk. This paper documents the proceedings of the expert panel and participant discussion held during the workshop.

Tyrosine phosphorylation profiling reveals the signaling network characteristics of Basal breast cancer cells.

To identify therapeutic targets and prognostic markers for basal breast cancers, breast cancer cell lines were subjected to mass spectrometry-based profiling of protein tyrosine phosphorylation events. This revealed that luminal and basal breast cancer cells exhibit distinct tyrosine phosphorylation signatures that depend on pathway activation as well as protein expression. Basal breast cancer cells are characterized by elevated tyrosine phosphorylation of Met, Lyn, EphA2, epidermal growth factor receptor (EGFR), and FAK, and Src family kinase (SFK) substrates such as p130Cas. SFKs exert a prominent role in these cells, phosphorylating key regulators of adhesion and migration and promoting tyrosine phosphorylation of the receptor tyrosine kinases EGFR and Met. Consistent with these observations, SFK inhibition attenuated cellular proliferation, survival, and motility. Basal breast cancer cell lines exhibited differential responsiveness to small molecule inhibitors of EGFR and Met that correlated with the degree of target phosphorylation, and reflecting kinase coactivation, inhibiting two types of activated network kinase (e.g., EGFR and SFKs) was more effective than single agent approaches. FAK signaling enhanced both proliferation and invasion, and Lyn was identified as a proinvasive component of the network that is associated with a basal phenotype and poor prognosis in patients with breast cancer. These studies highlight multiple kinases and substrates for further evaluation as therapeutic targets and biomarkers. However, they also indicate that patient stratification based on expression/activation of drug targets, coupled with use of multi-kinase inhibitors or combination therapies, may be required for effective treatment of this breast cancer subgroup.