Neoplastic Diseases & Cancer

Neoplastic Diseases & Cancer Definition of Neoplastic Diseases ●​ Abnormal mass of tissue formed when: ○​ Cells divide more than they should, or ○​ Cells fail to undergo programmed cell death (apoptosis) What is Cancer? ●​ A range of conditions defined by abnormal, disordered, and uncontrolled growth of cells. ●​ The type of affected tissue/cells defines individual cancer types. ●​ Characteristics: ○​ Originate in a single tissue type within an organ. ○​ Can grow locally or spread to distant organs (metastasis). Common Types of Cancers 1.​ Epithelial cells: Carcinomas 2.​ Mesodermal cells (bone/muscle): Sarcomas 3.​ Glandular tissues: Adenocarcinomas Hallmarks of Cancer 1.​ Autonomy from growth signals ○​ Mutations bypass normal growth factor signaling. 2.​ Evasion of growth inhibition ○​ Signal pathways regulating growth are reduced/ineffective. 3.​ Unlimited replication ○​ Cancer cells prevent telomere loss, bypassing replication limits. 4.​ Invasion and metastases ○​ Loss of adhesion and increased invasion enzymes. 5.​ Angiogenesis ○​ Cancer cells stimulate new blood vessel growth to sustain tumors. 6.​ Evasion of cell death (apoptosis) Enablers of Hallmarks ●​ Inflammation ●​ Genomic instability ●​ Mutations Clonal Nature of Cancer ●​ A single mutated cell can dominate tissue. ●​ Additional mutations may occur, leading to drug resistance. ●​ Consequence of DNA alterations: point mutations, deletions, rearrangements, translocations. Genetics Two-Hit Hypothesis ●​ First hit: Inherited defective tumor suppressor gene ●​ Second hit: Acquired loss of function in the normal allele Germline Mutations ●​ Mutations in egg/sperm DNA; heritable. Control of Cancer Cell Growth ●​ Proliferation ●​ Cell death: apoptosis, necrosis, autophagy ●​ Differentiation Differentiation ●​ How similar cancer cells are to normal tissue: ○​ Well-differentiated: slower-growing, less aggressive ○​ Poorly differentiated: immature, aggressive, poor prognosis Genetic Mutations ●​ Proto-oncogenes → Oncogenes:​ Mutations lead to higher levels or activity of protein products. ●​ Tumor suppressor genes:​ Mutations cause loss of growth inhibition. Epidemiology of Cancer ●​ Influencing factors: 1.​ Environment, diet, reproduction, alcohol, smoking ●​ Carcinogens: 1.​ Radiation (UV, ionizing) 2.​ Chemicals (e.g., benzopyrene, nitrosamines, alkylating agents) 3.​ Infections (HPV, HIV, EBV, H. pylori) Early Detection & Screening ●​ Screening identifies at-risk but asymptomatic individuals. ●​ HPV vaccination reduces cervical cancer risk. Chemotherapy Definition ●​ Drug-based treatment of cancer, targeting rapidly dividing cells. Cell Cycle Phases ●​ ●​ ●​ ●​ ●​ G0: Resting, specialized cells, resistant to chemotherapy G1: Protein/RNA synthesis S: DNA replication G2: RNA/protein synthesis continues; prepares for mitosis M: Cell division Classification of Chemotherapy ●​ Phase-specific: acts on a particular cell cycle phase ●​ Phase non-specific: acts on all but G0 ●​ Cycle non-specific: acts on all phases including G0 Growth Fraction ●​ Proportion of cells actively dividing. ●​ High growth fraction → more chemotherapy-sensitive Tumor Structure & Chemotherapy Response ●​ Necrotic center: dead cells due to poor blood supply ●​ Outer layer: invasive, accessible to drugs ●​ Hypoxic center: insufficient nutrients, may resist initial chemotherapy Log Kill Hypothesis ●​ Chemotherapy kills a constant fraction of cells per dose. ●​ Example: 1g tumor = 10⁹ cells; 99% kill → 10⁷ remain. Chemotherapy Agents Alkylating Agents & Platins ●​ Cross-link DNA, prevent repair, induce apoptosis ●​ Examples: Cisplatin, Carboplatin, Oxaliplatin Antimetabolites ●​ Purine/pyrimidine analogs (e.g., Methotrexate, Fluorouracil) ●​ Inhibit DNA synthesis Plant Alkaloids & Topoisomerase Inhibitors ●​ Vinca alkaloids: block mitotic spindle (e.g., Vincristine) ●​ Topoisomerase inhibitors: prevent DNA supercoiling (e.g., Irinotecan, Etoposide) Anthracyclines ●​ Intercalate DNA → inhibit replication, induce strand breaks ●​ Example: Daunorubicin Other Agents ●​ Asparaginase: depletes asparagine ●​ Interferons: immunomodulatory, anti-proliferative Hormones ●​ Glucocorticoids: lympholytic ●​ Tamoxifen: blocks estrogen in breast cancer ●​ GnRH analogs & Aromatase inhibitors: reduce sex hormones Monoclonal Antibodies ●​ Bind tumor-specific receptors → inhibit growth ●​ Can be conjugated with drugs/radiation for targeted therapy Adjunctive Agents ●​ Folinic acid: enhances effects of Fluorouracil and Methotrexate ●​ MENSA: prevents urothelial toxicity from oxazaphosphorines