Dive into cancer biology with our Week 1 notes. Learn about cancer's history, genetic basis (oncogenes, tumor suppressors), angiogenesis, metastasis, and i
WEEK 1 — Introduction to Oncology 1. History of Cancer Treatment Cancer has been known since ancient Egypt (Edwin Smith Papyrus, ~1600 BC) First surgery for cancer — 19th century First chemotherapy — mustard gas derivatives after WW2 (nitrogen mustards → first alkylating agents) Radiation therapy started early 1900s after discovery of X-rays Modern era = targeted therapy + immunotherapy (1990s–now) --- 2. Cellular & Genetic Basis of Cancer Cancer is basically uncontrolled cell division caused by DNA damage. Key genes involved: Gene Type Normal Role In Cancer --- --- --- Proto-oncogenes Promote normal cell growth Mutated → Oncogenes → cells divide uncontrollably Tumor suppressor genes Brake cell division (e.g. p53, RB) Deleted/mutated → brakes fail DNA repair genes Fix DNA errors Lost → mutations accumulate Hallmarks of cancer (Hanahan & Weinberg) — just know these: Sustains proliferative signaling Evades growth suppressors Resists cell death (apoptosis) Enables replicative immortality Induces angiogenesis Activates invasion & metastasis Evades immune destruction --- 3. Mechanism of Cancer Normal cell cycle: G1 → S → G2 → M → (repeat or G0) Cancer cells: Ignore checkpoints (especially G1/S checkpoint controlled by p53) Don't respond to apoptosis signals Produce their own growth factors Develop their own blood supply ( angiogenesis via VEGF) Can metastasize — invade basement membrane → enter blood/lymph → colonize distant organs --- 4. Introduction to Cancer Biology Carcinogenesis = the process of becoming cancerous. 3 stages: 1. Initiation — DNA mutation occurs (carcinogen exposure, radiation, virus) 2. Promotion — mutated cell gets a growth advantage, starts proliferating 3. Progression — more mutations accumulate, becomes malignant, invades Types of tumors: Benign — grows locally, doesn't invade or metastasize Malignant — invades tissues, can metastasize = cancer Naming: Carcinoma = epithelial origin (most common) Sarcoma = connective tissue Lymphoma/Leukemia = blood/lymph --- 5. Introduction to Immuno-Oncology The immune system normally kills cancer cells — mainly via T-cells (CD8+ cytotoxic T cells). Cancer evades immunity by: Downregulating MHC-I (so T-cells can't recognize it) Expressing PD-L1 → binds PD-1 on T-cells → T-cell "exhaustion" (turns off immune attack) Creating an immunosuppressive tumor microenvironment This is why checkpoint inhibitors work: Anti-PD-1 (Pembrolizumab, Nivolumab) — block PD-1 → T-cells stay active Anti-CTLA-4 (Ipilimumab) — another checkpoint, same idea Think of PD-1/PD-L1 as cancer pressing the "off switch" on your immune system. Checkpoint inhibitors remove that switch. --- Quick Recall Concept Key Point --- --- First chemo drug Nitrogen mustard (from mustard gas) Most important tumor suppressor p53 ("guardian of the genome") Angiogenesis mediator VEGF Cancer immune evasion PD-L1 → binds PD-1 → T-cell exhaustion 3 stages of carcinogenesis Initiation → Promotion → Progression