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Metastatic Cancer - Coggle Diagram
Metastatic Cancer
How are tumors treated?
Resection (surgery)
Radiotherapy: DNA damage has largest effect on rapidly dividing cells
Chemotherapy: Kills rapidly dividing cells
Targeted therapies (i.e. inhibitors of growth factor receptors, MAPKinases)
Immunotherapies: autoimmune deficiences contribute to cancer
Patient specific combination therapies
Not all tumors progress to life threatening cancer
ex. Korea routinely removed thyroid glands in an effort to detect thyroid cancer --> NO impact on mortality rate
Identifying a BENIGN tumor as carcinogenic ("overdiagnosis")
not sufficient info to see if tumor is cancerous and harmful or not
If after treatment: no evidence of cancer cells
ex. radiotherapy after breast tumor resection
only 1/4 of women benefited from the treatment
Progress against human disease: overall cancer mortality rate has decreased
major reasons cancer rate is falling: people quit smoking, curing stomach ulcers using antibiotics
Breast cancer and CRC mortality rates are dropping because of better detection and treatment options
What factors influence relapse after cancer treatment (metastasis)?
one notion: cancers are diseases of renegade cells (cancer cells) that divide, grow, develop, migrate in an unregulated manner
Why do these cells divide?
mitogens drive cell proliferation
tumor cells:
secrete "own" growth factor
have RTK or signaling kinase ON all the time: HER2 BRAF
express version of RAS that can't shut itself off
invasion of tumor cells (carcinomas) involves transition from an epithelial layer
STEPS IN METASTASIS
primary tumor formation
localized invasion (tumor moves out of original location)
intravasation (moves into bloodstream and interacts with platelets, lymphocytes, other blood components)
transport through circulation to microvessels in various organs
1 more item...
Is cancer development linear? Not always
Dessiminated tumor cells
At all stages of development there's potential for tumor cells to move out of primary tumor and travel throughout body (don't need a fully grown primary tumor to form metastasis)
Test when cancer cells far from tumor can be detected
Modify mouse: RAS is always ON, tumor suppressor is deleted (p53)
measure rate of metastasis and cell growth at distant sites
Cancer cells can instruct OTHER cells to support growth of tumor
"Host cells" at site of metastasis are important for metastasis ability to grow, thrive, spread
Ability to establish metastases is controlled by non-cancer cells
How do we find "host" factors that help block metastasis? Genetic screens
Strategy: inject metastatic melanoma cells into 810 mutant mice strains (each mutant mice has specific mutant gene - lack of a specific protein), look for metastasis
look for metastasis (count)
ex. of gene found: Spns2: Regulation of epithelial barriers and immune system activation: contribution to a hostile environment in lungs for melanoma cells
if lungs had an INCREASED number of metastases relative to WT mouse, then that gene that was KO is important for blocking metastasis