Cyclin-dependent kinases (CDKs) have been pursued for more than a decade for the treatment of cancer. CDK inhibitors are expected to slow the rate of cell division and potentially increase the apoptotic fraction of rapidly dividing cells. Although CDK activity is often increased in tumors, normal dividing tissues are also susceptible to the cytostatic and cytotoxic effects of CDK inhibitor action. Therefore the typical toxicity profile associated with cytotoxic anti-cancer therapy, bone marrow suppression and gastrointestinal toxicity, is expected with CDK inhibitors. Bone marrow toxicity and the ensuing delayed peripheral leukocyte suppression often limit the therapeutic application of cytotoxic anticancer drugs. Here we characterize an unusual bone marrow-independent acute toxicity toward leukocytes from broad spectrum CDK inhibitors in monkeys and rodents. The potential combination of both acute and delayed immunosuppression would likely further restrict the application of these particular compounds. Since the cells targeted were non-proliferating, it was assumed that the toxicity was not driven by the intended pharmacological mechanism thereby facilitating the development of a testing strategy to identify compounds with a reduced potential for acute leukocyte toxicity. This testing strategy resulted in a CDK inhibitor void of bone marrow-independent leukocyte toxicity that is currently undergoing clinical testing.
Thoroughly reviewing the literature on developmental progress assessment, St. Onge et al. outline how explicitly mapping student development can help programs, students, and faculty.
The COVID-19 pandemic caused substantial disruptions in medical education. The University of British Columbia (UBC) MD Undergraduate Program (MDUP) is the sixth-largest medical school in North America. MDUP students and faculty developed a joint response to these disruptions to address the curriculum and public health challenges that the pandemic posed.
Implication Statement:
Given the efficacy of simulations as a medical education tool, the inability to provide them during the COVID-19 pandemic may be detrimental to pre-clinical medical student learning. We developed hybrid simulations, where remote learner participants could direct an in-person assistant. This offered a learning opportunity that was more realistic than fully virtual simulations and abided by public health guidelines. Hybrid simulations provided an opportunity for medical students to practice real-time clinical decision making in a remote, high-fidelity, simulated environment. This approach could be adapted for rural healthcare students and professionals to participate in simulations without a local simulation centre.
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