Objectives	To describe: The central role of molecular alterations in cancer biology and evolution that play a role at all stages of tumorigenesis and are one of the largest areas of interest in pharmacologic targeting in cancer The increasing role for targeting tumour characteristics and molecular alterations that are shared among different cancer types and understand how these pathways relate to the mechanisms of action of certain anti-cancer drugs
Key Concepts	Distinguish commonly mutated tumour suppressor and oncogenes involved in tumour development and progression Explain the basis for therapeutic targeting of molecular mutations in tumours and the various mechanisms of pharmacologic intervention Define the importance of molecular oncology in the diagnosis, prognosis, and selection of therapeutic options in solid and haematologic malignancies Describe the concept of tumour molecular heterogeneity and how tumour evolution results in molecular differences in different areas within the same tumour lesion or between different tumour lesions of a same patient Demonstrate an understanding that some molecular alterations will be present from the onset of the tumour cell, whereas others will emerge over time as a result of selective pressure Recognise there are shared molecular alterations across tumour types of different origin and that these mutations may result in common therapeutic targets across classes Demonstrate an understanding of the downstream signalling cascade of intracellular kinase transcription factors as this relates to therapeutic targets, treatment failure, and development of resistance Determine the concepts of pathway up/down regulation and molecular pathways cross-talk or co-regulation Recognise that beyond gene mutations, the activity of a relevant pathway may be modified by transcriptional or epigenetic regulation Interpret the secondary mutational mechanisms and epigenetic modifications tumours make in response to therapy that lead to treatment resistance Give examples of certain pathognomonic chromosomal translocations that define various lymphoid malignancies and how this can be used for diagnosis Determine the importance of tumour suppressor gene functional deficiency in terms of DNA repair mechanisms as a marker for sensitivity to poly (ADP-ribose) polymerase inhibition and DNA damaging agents Interpret advanced molecular testing through FISH, cytogenetic, and next generation sequencing as it relates to appropriate diagnosis and treatment planning Determine that mutation in TP53 is the most common molecular alteration in cancer and conveys a worst prognosis than tumours with normal expression Recognise that though increasing in importance and frequency, the number of patients with targetable mutational changes with available therapeutic agents is very limited and most mutations are not currently targetable Identify that globally, infectious diseases are a major contribution to molecular alterations that lead to cancer with EBV, Hepatitis B and C, and HIV as major contributors to malignancy globally
Skills	Demonstrate the ability to: Apply the knowledge of biologic pathways to understand the drivers of cancer progression upon the presence of different molecular alterations Apply selection of advanced molecular testing of tumours for precise diagnosis and identification of therapeutic options Select molecular alterations associated with common familial cancer syndromes as a means for risk reduction in patients and their relatives