Technology advancement and the courage to challenge dogma have been key elements that have continuously shifted druggability limits. We illustrate this notion with several recent cancer drug-discovery examples, while also giving an outlook on the opportunities offered by newer modalities such as chemically induced proximity and direct targeting of RNA. Treatment resistance is a major impediment to the goal of durable efficacy and cure, but the confluence of new biological insights, novel drug modalities, and drug combinations is predicted to enable transformative progress in this decade and beyond.The upcoming decade of precision medicine for cancer is moving from the translation of specific genetic findings into clinically relevant improvement to the qualitative analyses of the genomic and immune tumor microenvironment, for an integrated treatment strategy in both metastatic and early disease.Advances in genomic science have transformed our ability to interrogate cancer, revealing biases that drive disparities in minority populations. Cancer disparities research engages diverse ethnic group inclusion as a matter of rigor, to address underrepresentation in genomic data sources, and has led to groundbreaking work, enhancing our understanding of tumor biology.Cancer models have helped solve many mysteries of cancer research, and are poised to bring our understanding to the next level as we dissect the relevance of cancer-associated alleles and heterocellular interactions. However, the ability of cancer models to correctly identify new therapeutic methods has been less fruitful, and a reconsideration of model designs and model applications should help develop more effective approaches for patients.In the next 10 years, gene-engineered T-cell therapies have the potential to provide broad benefit for the treatment of patients with cancer. Advances in immunology, molecular biology, and bioengineering allow the design of gene-engineered T cells that actively target metastatic lesions, specifically recognize and kill cancer cells, and maintain long-term immunologic memory. The quality of ethics consults is notoriously difficult to measure. Survey-based assessments cannot capture nuances of consultations. To address this gap, we conducted interviews with health professionals who requested ethics consults during the initial phase of the COVID-19 pandemic. Healthcare professionals requesting ethics consultation between March 2020 and May 2020 at a tertiary academic medical centre were eligible to participate. We asked participants to comment on the consults they called and thematically analysed responses to identify features associated with optimal quality consultations. Of 14 healthcare providers, 8 (57%) were women and professions were as follows 11 (79%) medical doctors, 1 (7%) social worker, 1 (7%) physician assistant and 1 (7%) nurse practitioner. Two aspects of quality emerged satisfaction and value. Themes within the domain of satisfaction included responsiveness of the ethics consultant, willingness to consult, institutional role of the ethics service and identifyingas implications for ethics consultation services more broadly. Ethics consultation-emphasising both the process and outcome-created valuable moral spaces, promoting thoughtful and ethical responses to dilemmas in patient care. Future assessments should incorporate patient and family/surrogate perspectives and explore the domain of education as an additional quality measure.Health research ethics (HRE) training programmes are being developed and implemented globally, often with a goal of increasing local capacity to assure ethical conduct in health-related research. Yet what it means for there to be sufficient HRE capacity is not well-defined, and there is currently no consensus on outcomes that HRE training programmes should collectively intend to achieve. Without defining the expected outcomes, meaningful evaluation of individual participants and programmes is challenging. In this article, we briefly describe the evolution of formal education in HRE, articulate the need for a framework to define outcomes for HRE training programmes, and provide guidance for developing HRE competency frameworks that define outcomes suited to their contexts. We detail critical questions for developing HRE competency frameworks using a six-step process (1) define the purposes, intended uses and scope of the framework; (2) describe the context in which practice occurs; (3) gather data using a variety of methods to inform the competency framework; (4) translate the data into competencies that can be used in educational programmes; (5) report on the competency development process and results and (6) evaluate and update the competency framework. We suggest that competency frameworks should be feasible to develop using this process, and such efforts promise to contribute to programmatic advancement.This paper considers the proposal to pay people to get vaccinated against the SARS-CoV-2 virus. The first section introduces arguments against the proposal, including less intrusive alternatives, unequal effects on populations and economic conditions that render payment more difficult to refuse. The second section considers arguments favouring payment, including arguments appealing to health equity, consistency, being worth the cost, respect for autonomy, good citizenship, the ends justifying the means and the threat of mutant strains. The third section spotlights long-term and short-term best practices that can build trust and reduce 'vaccine hesitancy' better than payment. The paper concludes that people who, for a variety of reasons, are reluctant to vaccinate should be treated like adults, not children. Laduviglusib Despite the urgency of getting shots into arms, we should set our sights on the long-term goals of strong relationships and healthy communities. SLE displays large clinical heterogeneity that beyond genetic factors may be determined by environmental exposures. In this Danish nationwide study, we aimed to determine if clinical subsets of SLE were associated with smoking history. At each of six participating centres, incident or prevalent inpatients and outpatients with SLE were consecutively included. Manifestations forming the basis of SLE classification were registered in an electronic chart system. Patients also provided questionnaire-based data on environmental exposures, including smoking history. Hierarchical cluster analysis was conducted to determine and characterise subsets of patients with similar traits of disease manifestations. Levels of smoking exposure by pack-years were correlated to the identified SLE subsets, as well as discrete SLE manifestations. The cohort consisted of 485 patients (88% women and 92% Caucasian) with SLE of which 51% were ever smokers. Common disease manifestations comprised non-erosive arthritis (81%), malar rash (57%), lymphopenia (55%), photosensitivity (50%) and persistent proteinuria (41%).