Key Pathophysiological Concepts

Why This Matters

Cancer pathophysiology is foundational to nursing practice because it explains why tumors behave the way they do—and more importantly, how you can anticipate complications, understand treatment rationales, and educate patients effectively. You're being tested on your ability to connect molecular mechanisms to clinical presentations, whether that's explaining why a tumor became resistant to chemotherapy or why metastatic disease appears in specific organs. These concepts show up repeatedly in questions about oncology nursing, pharmacology, and patient education.

The key to mastering this content isn't memorizing definitions in isolation—it's understanding the relationships between concepts. How does a mutation in a tumor suppressor gene lead to cell cycle dysregulation? Why does the tumor microenvironment matter for treatment resistance? Don't just know what cancer stem cells are; know why they make recurrence more likely. Each concept below illustrates a principle you'll need to apply clinically.

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Cellular Transformation: How Normal Cells Become Cancerous

Cancer begins at the cellular level when normal regulatory mechanisms fail. The transformation from healthy cell to malignant cell involves accumulated genetic damage that disrupts the balance between cell growth and cell death.

Definition of Cancer and Carcinogenesis

• Cancer is a group of diseases—not a single entity—characterized by uncontrolled cell growth that can invade surrounding tissues
• Carcinogenesis describes the multi-step transformation process where normal cells acquire mutations that progressively disable growth controls
• Contributing factors include genetic predisposition, environmental exposures (chemical carcinogens, radiation), and modifiable lifestyle choices like smoking and diet

Tumor Suppressor Genes and Proto-Oncogenes

• Tumor suppressor genes act as brakes—they normally slow cell division; mutations cause loss of function, removing critical growth inhibition
• Proto-oncogenes act as accelerators—when mutated into oncogenes, they become stuck in the "on" position, driving continuous proliferation
• Both gene types maintain cellular homeostasis—cancer typically requires dysfunction in multiple genes from both categories (the "two-hit hypothesis")

Genetic and Epigenetic Alterations in Cancer

• Genetic alterations include point mutations, chromosomal deletions, and gene amplifications that directly change DNA sequences
• Epigenetic changes modify gene expression without altering DNA sequence—DNA methylation can silence tumor suppressors while histone modifications alter chromatin accessibility
• Both mechanisms are clinically relevant—epigenetic changes are potentially reversible, making them therapeutic targets

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Hallmarks of Malignancy: What Makes Cancer Cells Different

Cancer cells acquire specific capabilities that distinguish them from normal cells. These "hallmarks" represent the functional changes that allow tumors to grow, survive, and spread.

Hallmarks of Cancer Cells

• Sustaining proliferative signaling—cancer cells produce their own growth signals or amplify responses to external signals, creating self-sufficiency
• Evading growth suppressors—mutations disable checkpoint proteins like p53 and Rb, removing normal "stop" signals
• Resisting cell death—cancer cells upregulate survival pathways, allowing them to persist despite damage that would trigger apoptosis in healthy cells

Cell Cycle Dysregulation in Cancer

• Checkpoint mutations allow cells to progress through $G_1$, $S$, and $G_2$ phases without proper DNA verification
• Accelerated division reduces time for DNA repair, compounding genetic instability with each replication cycle
• Key regulators affected include cyclins, cyclin-dependent kinases (CDKs), and checkpoint proteins—many chemotherapies target these pathways

Apoptosis Evasion in Cancer Cells

• Anti-apoptotic proteins like Bcl-2 are often overexpressed, blocking the intrinsic death pathway
• Pro-apoptotic factors such as Bax and p53 are frequently downregulated or mutated, disabling death signals
• Clinical significance—apoptosis resistance explains why some tumors don't respond to chemotherapy; newer therapies target these survival mechanisms directly

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DNA Integrity: Repair Failures and Mutation Accumulation

Genomic stability depends on functional repair mechanisms. When these systems fail, mutations accumulate and drive cancer progression.

DNA Repair Mechanisms and Their Dysfunction

• Normal repair pathways include mismatch repair, nucleotide excision repair, and homologous recombination—each corrects specific damage types
• Defective repair in cancer leads to mutation accumulation and genomic instability, accelerating tumor evolution
• Therapeutic implications—tumors with BRCA mutations (defective homologous recombination) respond to PARP inhibitors through synthetic lethality

Carcinogen Types and Their Effects

• Chemical carcinogens (tobacco smoke, aflatoxins) cause direct DNA damage or form DNA adducts that lead to replication errors
• Physical carcinogens like UV and ionizing radiation induce strand breaks, base modifications, and chromosomal rearrangements
• Biological carcinogens include oncogenic viruses (HPV, Hepatitis B) that integrate into host DNA or produce proteins that inactivate tumor suppressors

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Tumor Growth and Survival: The Supportive Environment

Tumors don't grow in isolation—they actively modify their surroundings to support continued expansion. Understanding these interactions explains treatment resistance and identifies therapeutic targets.

Angiogenesis in Tumor Growth

• Tumors require blood supply—once a tumor exceeds 1-2 mm, diffusion alone cannot supply adequate oxygen and nutrients
• VEGF (vascular endothelial growth factor) is the primary signal cancer cells secrete to stimulate new vessel formation
• Anti-angiogenic therapies like bevacizumab target this pathway, though tumors often develop resistance through alternative signaling

Tumor Microenvironment

• Components include cancer-associated fibroblasts, immune cells, blood vessels, and extracellular matrix—all influencing tumor behavior
• Bidirectional communication occurs through cytokines, growth factors, and direct cell contact, promoting invasion and therapy resistance
• Clinical relevance—the microenvironment explains why the same cancer type behaves differently in different patients and locations

Inflammation and Cancer Development

• Chronic inflammation creates a pro-tumor environment—inflammatory mediators like NF-κB and COX-2 promote cell survival and proliferation
• Inflammatory cells release reactive oxygen species causing DNA damage, plus growth factors supporting tumor expansion
• Prevention implications—anti-inflammatory strategies (aspirin use in colorectal cancer prevention) represent an active research area

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Immune Interactions: Surveillance and Escape

The immune system can recognize and eliminate cancer cells, but tumors develop sophisticated evasion strategies. This cat-and-mouse relationship is the foundation of immunotherapy.

Immune System's Role in Cancer

• Immunosurveillance allows T cells and NK cells to identify and destroy cells displaying abnormal antigens or stress signals
• Immune checkpoint proteins like PD-1 and CTLA-4 normally prevent autoimmunity but can be exploited by tumors to "turn off" attacking immune cells
• Immunotherapy revolution—checkpoint inhibitors (pembrolizumab, nivolumab) release these brakes, restoring anti-tumor immunity

Cancer Stem Cells

• Cancer stem cells (CSCs) represent a small subpopulation with self-renewal capacity and the ability to regenerate the entire tumor
• Treatment resistance occurs because CSCs are often quiescent (not actively dividing), making them invisible to chemotherapies targeting rapid division
• Recurrence mechanism—even when bulk tumor is eliminated, surviving CSCs can repopulate the tumor months or years later

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Progression and Spread: From Local to Systemic Disease

Cancer staging reflects a biological continuum from localized growth to widespread metastasis. Understanding this progression informs prognosis and treatment intensity.

Stages of Cancer Progression

• Initiation involves the first genetic mutation creating a cell with malignant potential—this may remain dormant for years
• Promotion occurs when initiated cells receive signals (hormones, growth factors, inflammation) that stimulate clonal expansion
• Progression represents acquisition of additional mutations enabling invasion, metastasis, and treatment resistance—the hallmark of malignant transformation

Metastasis Process and Stages

• The metastatic cascade includes local invasion → intravasation → circulation survival → extravasation → colonization at distant sites
• Metastatic inefficiency—millions of cells may enter circulation, but less than 0.01% successfully establish secondary tumors
• Organ tropism explains preferential spread patterns (breast cancer to bone, colon cancer to liver)—determined by circulation patterns and microenvironment compatibility

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Quick Reference Table

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Self-Check Questions

1. A patient asks why their tumor stopped responding to chemotherapy. Which two concepts best explain treatment resistance, and how do their mechanisms differ?

2. Compare and contrast tumor suppressor genes and proto-oncogenes: What type of mutation affects each, and how does this distinction influence targeted therapy approaches?

3. A tumor biopsy shows high VEGF expression and extensive new blood vessel formation. Which pathophysiological concept does this illustrate, and what therapeutic strategy might target it?

4. Why might a patient experience cancer recurrence years after achieving complete remission with chemotherapy? Identify the concept involved and explain the underlying mechanism.

5. If an exam question describes a patient with Lynch syndrome (hereditary nonpolyposis colorectal cancer), which pathophysiological concept is being tested, and how does this inherited condition increase cancer risk?