Cancer Chemo Overview

University:
University of Wolverhampton
Course:
4PY019 | Pharmacy
Academic year:

2024
Views:

241

Pages:

3
Author:

Carisma W.

Cancer and Chemotherapy – Detailed Overview 1. Common Cancers 1.1 Males 1. Prostate 2. Lung 3. Large bowel 1.2 Females 1. Breast 2. Lung 3. Large bowel 1.3 Solid Tumours • Carcinomas • Sarcomas • Mesotheliomas • Gliomas • Germinomas 1.4 Non-Solid Tumours • Leukemias • Lymphomas 2. Characteristics of Cancer Cells • De-differentiation • Immortalisation • Invasiveness • Metastasis • Uncontrolled cell division 3. Causes of Cancer • Chemical (tobacco, alcohol, high salt/nitrates, chemotherapy) • Radiation (UV light, ionising radiation, radon gas, X-rays) • Biological • Viruses: Epstein-Barr, HPV, Hep B/C (direct); HIV (indirect) • Bacteria: Helicobacter pylori 1 4. Chemotherapy Basics • Damages DNA, inhibits new DNA synthesis, stops mitosis • Targets cycling tumour cells (growth fraction) • Resistance if tumour has non-cycling cells • Proteins often targeted: topoisomerases, helicases • Combination chemotherapy: decreases toxicity, maximizes cell kill, synergistic action, reduces resistance 5. Side Effects of Chemotherapy • Nausea, vomiting, GIT disturbances • Bone marrow suppression (myelosuppression) • Immunosuppression • Alopecia • Teratogenicity 6. Classes of Anti-Cancer Drugs 6.1 Antimetabolites • Folic acid antagonists: Methotrexate, Pemetrexed, Raltitrexed • Pyrimidine analogues: Fluorouracil, Cytarabine, Capecitabine • Purine analogues: Mercaptopurine, Thioguanine, Cladribine 6.2 Alkylating and Platinating Agents • Nitrogen mustard: effective in lymphocyte cancers • Nitrosoureas: lipid soluble, cross BBB, negative effect on bone marrow • Platinating agents (Cisplatin): cross-link DNA (guanine), nephrotoxic, used with ondansetron 6.3 Anti-Tumour Antibiotics • Anthracyclines (Doxorubicin): intercalates DNA, inhibits topoisomerase II, cardiac toxicity • Dactinomycin: intercalates DNA, inhibits transcription; used in Wilms tumour, sarcomas • Bleomycin: induces DNA strand breaks (G2/M phase); pulmonary fibrosis • Mitomycin C: DNA crosslink; gastric/anal cancers; myelosuppression, nephrotoxicity • Procarbazine: interferes with DNA/RNA synthesis; Hodgkin's lymphoma • Hydroxycarbamide: inhibits ribonucleotide reductase; CML 6.4 Plant-Derived Agents • Vinca alkaloids: anti-mitotic, anti-microtubules; non/Hodgkin's lymphoma • Taxanes: freeze microtubules; breast, lung, ovarian cancers; Docetaxel → leg edema • Etoposide: topoisomerase II inhibitor; lung, stomach, NHL, testicular • Camptothecins: topoisomerase I inhibitor; colorectal, small cell lung cancer 2 7. Key Genetics Concepts • High-risk genes: BRCA1/2 → 75% chance breast/ovarian cancer • HNPCC mutation → increased colorectal cancer risk • DNA: base pairs bound by hydrogen bonds; mRNA: T → U; start codon AUG; stop codons UAA, UAG, UGA • DNA packaged around nucleosomes; normal cells in G0; growth fraction = proportion of dividing tumour cells 8. Eukaryotic DNA Replication 1. ORC binds replication origins 2. Recruits proteins (topoisomerases, helicases) forming pre-replication complex 3. Helicases unwind DNA → replication forks 4. Topoisomerases cut/rejoin DNA 9. Rationale for Combination Chemotherapy • Decrease toxicity (lower dose of each agent) • Maximise tumour cell kill • Synergistic action (one drug enhances another) • Reduce tumour resistance 3