03/02e Neoplasia IV Flashcards
What are the three pathways of metastasis?
1) Seeding body cavities (peritoneum, pleura, meninges)
2) Lymphatic spread
3) Hematogenous spread to liver, lung, brain, and bone
What are the four steps to invasion of the extracellular matrix?
1) Loosening of intercellular junctions
2) Attachment to extracellular matrix
3) Degradation of the basement membrane
4) Migration through the basement membrane
What is required for tumors to grow in size?
Angiogenesis
How do tumors initiate angiogenesis?
Make angiogenesis factors like VEGF, HIF
Why is tumor angiogenesis such an attractive therapeutic target? Describe three reasons
Tumor endothelial cells are very distinct from normal cells
Readily accessible to therapeutic agents (because they are in the blood)
Tumor endothelial cells are genetically stable - should not develop resistance
What is a cancer chemotherapeutic that targets tumor endothelial cells?
Bevacizumab (Avastin)
What is some further evidence that metastasis is REALLY HARD?
Many patients with cancer have circulating tumor cells, but never develop distant metastases
Even patients with thousands of circulating tumor cells typically develop only a few metastases
What evidence supports the idea that the immune system defends against cancer?
1) Immunosuppressed patients have markedly higher incidence of many cancers
2) Cancer patients develop measurable immune responses to tumor antigens
3) Lymphocytes seen histologically in and around cancers (tumor-infiltrating lymphocytes)
4) Well-documented examples of some cancers undergoing complete regression, even when metastatic - site is replaced by lymphocytes and macrophages
What types of tumors are vastly more common in immunosuppressed patients?
Viral-related tumors (HPV, EBV, Kaposi’s) and skin cancers
What are some common tumor antigens against which we can raise an immune defense? List six
1) Products of mutated oncogenes or tumor suppressor genes and fusion proteins
2) Overexpressed or aberrantly expressed self proteins
3) Oncogenic viral proteins
4) Oncofetal antigens
5) Altered cell surface glycolipids and glycoproteins
6) Cell type-specific differentiation antigens
What does it mean for the course of the disease if lymphocytes are seen around cancers histologically?
Improved prognosis!
What are the tenets of the Immune Surveillance Theory?
Very early cancers are usually eliminated by the immune system
To be successful, a tumor must evade the host immune system
By what three mechanisms do tumor cells evade the immune system?
Suppress antigen expression
Disrupt the MHC I signaling system
Express immunosuppressive cytokines
What are some examples of available immune therapies?
Monoclonal antibodies - Herceptin for breast cancer, Rituximade for B-cell lymphomas
Immune adjuvants - BCG for bladder cancer
Cytokines - interferon for kidney cancer and melanoma
Donor vs. host - donor leukocyte infusion attacks hosts cancer cells as foreign
“Vaccine” - patient’s dendritic cells cultured in vitro with a sample of tumor to induce immunity
What are the effects of neoplasia on the host?
Local symptoms - depending on the location of the tumor, it can compress surrounding tissues and cause chronic or acute symptoms
Metastatic symptoms - also depends on location (enlarged lymph nodes and liver, cough and hemoptysis, neurological symptoms, fractured bones)
Systemic symptoms - appetite, endocrine, energy, etc.
