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Dermatology
Principles of Cutaneous Tumor Biology
Built from Dermatology, 5th Edition
What’s inside
6 sections · 94 slides
Overview
- Why skin cancer research matters
- Three levels of cancer biology
- The evolution of cancer hallmarks
- History of conceptual advances in cancer biology
The Genome Perspective
How DNA damage builds up and gets selected during cancer development
- The DNA sequencing revolution
- Landmark genome projects
- Structural genomic alterations
- Types of somatic mutations
- Mutations classified by size
- Structural variation and karyotype changes
- Oncogenes: mutations that switch signals on
- Tumor suppressor genes: losing the brakes
- Oncogenes versus tumor suppressor genes
- Loss of heterozygosity in tumor suppressor genes
- The Darwinian model of gradual evolution
- Reading a tumor's mutational history
- Driver mutations versus passenger mutations
- Hotspot mutations in known cancer genes
- Genomic aberrations seen in cancer
- Chromothripsis: genome shattering
- Chromoplexy and kataegis
- Gradual versus punctuated genome evolution
- Gradual versus punctuated cancer genome evolution
- Cancer evolution begins earlier than expected
- Evolution differs by melanoma subtype
The Cell Perspective
How driver mutations rewire a single cell's behavior
- Functional capabilities acquired by cancer cells
- Hallmark capabilities of cancer cells
- Sustained proliferative signaling
- Ras mutations lock the growth switch on
- BRAF inhibitors and the MAPK pathway
- Deregulated metabolism: the Warburg effect
- Oncogenic signaling drives metabolic rewiring
- Cell cycle control by p53 and Rb
- Cell cycle checkpoints and error-prone replication
- p53: guardian of the genome
- CDKN2A and Rb: losing the G1/S brake
- Resisting cell death: senescence
- Apoptosis: programmed cell death
- Apoptotic signaling pathways
- Newer forms of programmed cell death
- Genome instability and aneuploidy
- Aneuploidy and innate immune sensing
The Tissue Perspective
How mutant cells reorganize the surrounding tissue into a tumor ecosystem
- Disrupted tissue architecture in cancer
- A dysregulated communication network
- The tumor as a dynamic ecosystem
- Skin stem cells and tissue renewal
- Injury triggers a plastic, adaptable state
- UV injury, tissue repair, and cancer development
- Hedgehog and Notch guide tissue repair
- Avoiding immune destruction
- Immune checkpoint blockade breakthrough
- How the immune system spots cancer cells
- Self-antigens and cancer testis antigens
- How tumors evade immune attack
- Immune recognition and the metastatic process
- Cancer-promoting inflammation
- A double-edged inflammatory pathway
- Chromosomal instability drives a vicious cycle
- Inducing new blood vessels (angiogenesis)
- Abnormal tumor blood vessels
- Invasion and metastasis: the "seed and soil" idea
- Epithelial-to-mesenchymal transition (EMT)
- The metastatic cascade
- Metastasis-initiating cells
- Genomic changes in metastatic disease
Pathogenesis of Keratinocyte Carcinomas
How basal cell and squamous cell carcinoma develop at the molecular level
- Basal cell versus squamous cell carcinoma
- The highest mutation burden of any cancer
- Discovering BCC's molecular cause
- The Hedgehog signaling pathway
- The Hedgehog signaling pathway
- Targeting Hedgehog signaling in BCC
- BCC's fuller driver mutation landscape
- Molecular pathogenesis and evolution of BCC
- Modeling cSCC in mice
- Discovering the Notch pathway
- The Notch signaling pathway
- Notch: cancer-promoting in some tissues, protective in skin
- cSCC's driver mutation landscape
- Molecular pathogenesis and evolution of cSCC
- The evolutionary trajectory of cSCC
Current Developments and Future Perspectives
New technologies shaping the next stage of cancer research and care
- Mapping cancer ecosystems in space and time
- Toward a cancer-specific tissue atlas
- The microbiome and cancer
- Bringing molecular profiling into the clinic
- Key takeaways
- References
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- Dermatology, 5th Edition (2-Volume Set)