Objectives
  • To be able to critically consider and clinically apply newly proposed and existing models referring to molecular/cellular mechanisms of disease, modes of action of specific drugs, significance of biomarkers, as well as potential bases of adverse effects and acquired resistance to specific treatments

Awareness
  • Awareness of the organisation of biological systems in multicomponent networks and availability of signal transduction pathways and protein–protein interaction maps linking protein complexes to specific functions of cancer cells

  • Awareness of the availability of high-resolution maps and nucleotide sequences of all human chromosomes, including epigenetic marks and genomic aberrations prevalent in various types of tumours

  • Awareness of the availability of custom, high-throughput analyses of full exome sequences able to identify putative driver mutations in solid or liquid specimens

  • Awareness of the availability of mouse models of many driver mutations, including some combinations of oncogenic mutations

  • Awareness of accessible technologies permitting establishment of in vitro cultures, as well as tumour implants derived from patient specimens and available for screening of individual drugs or drug combinations

  • Recognition of the importance of liquid biopsies as sources of early indicators of relapse and emergence of new mutations

Knowledge
  • Familiarity with mechanisms underlying stepwise transition from a normal cell to a malignant cell, along with their relevance to mutations affecting tumour suppressor genes, oncogenes, DNA repair systems or immune checkpoints

  • Understanding of the exact tissue of origin of a cancer cell, the heterogeneity of epithelial and other cell lineages within all tissues, as well as relations of cancer cells to the linear transition from a stem cell to progenitors and, eventually, to differentiated cells

  • Familiarity with the complex and variable tumour-to-stroma interactions and the cellular heterogeneity of the host tissue, including the extracellular matrix and neighbouring non-cancerous cells (eg, fat cells, fibroblasts and various lymphoid and myeloid cells)

  • Understanding of the coexistence within cancer cells of mutually interacting networks that process information (signalling), substances (metabolic) and ATP (energy), to maintain homeostasis

  • Familiarity with the control of gene expression by epigenetic, transcriptional and post-transcriptional processes, including covalent modifications of DNA and chromatin, as well as regulation by non-coding RNAs

  • Familiarity with phases and checkpoints of the cell cycle, their regulation by growth factors and control by protein complexes involved in carcinogenesis, as well as inhibition by apoptosis-inducing radio- and chemotherapeutic modalities

  • Understanding of basic biochemical and molecular biological techniques, including polymerase chain reaction (PCR) to be inserted, western blots, immunofluorescence (IF), transgenic animal procedures and mass-spectrometry of proteins and metabolites

  • Understanding of the mechanisms of drug resistance due to compensatory responses and emergence of new mutations

  • Understanding of the terminology of biological systems, network biology and features conferring functional robustness to biological systems while exposing vulnerabilities of cancer

Skills
  • Ability to use information technology and data sets to understand the big landscape of disease and patient care

  • Ability to discuss critically pharmacological interception strategies (eg, kinase inhibitors and monoclonal antibodies) and potential adverse effects based on cellular maps of signalling and metabolism, as well as phenotypes of genetically engineered animals

  • Ability to discuss critically tumour heterogeneity and Darwinian evolution of rare, pre-existing clones in the face of environmental stress (eg, metastasis to a new tissue environment and switching to a new therapeutic modality)