Download Cancer Therapies

Cancer Therapies
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DNA microarrays are used to assess the relative
expression of thousands of genes simultaneously—relative
expression means that two things are being compared
relative to one another.
e.g., Normal B Cells
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e.g., NHL Cells
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Figure 10-33 (part 1 of 2) Essential Cell Biology (© Garland Science 2010)
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• Some tumors will never advance. Treating
them is a waste of resources.
• Some tumors are highly-aggressive and have
probably already advanced to the point of
metastasis by the time they’re diagnosed.
Treating them is a waste of resources; it just
delays the inevitable.
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• Some tumors that have not yet advanced to
the point of invasiveness can be removed
surgically and require no additional treatment.
General Categories of Cancer Treatments:
Surgery
Radiation
Chemotherapy
Targeted therapy
Biologics
Immunotherapy
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Stem Cell therapy
General Categories of Cancer Treatments:
Surgery
Radiation
Chemotherapy
Targeted therapy
Biologics
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Surgery
What?
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• Open or minimally invasive
• Remove tumor + adjacent healthy tissue +/- regional lymph tissue
• Limited to solid tumors
Why?
• To remove tumor completely
• To “debulk”
 Relieve symptoms
 Can increase effectiveness of other treatment(s)
Downsides:
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Potential pain
Potential infection
Potential death
Cost
General Categories of Cancer Treatments:
Surgery
Radiation
Chemotherapy
Targeted therapy
Biologics
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Radiation Therapy
What?
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• External Beam Radiation
• Internal (Brachytherapy)
 Permanent
 Cyclic
• Systemic
• Adjuvant vs Neoadjuvant
Radiation Therapy
What?
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• External Beam Radiation
• Internal (Brachytherapy)
 Permanent
 Cyclic
• Systemic
• Adjuvant vs Neoadjuvant
Radiation Therapy
Why?
• To induce DNA double-strand breaks
• To generate “free radicals”
 To kill cells
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Radiation Therapy
Downsides
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Effects not immediate (cells die over weeks  months)
Fatigue
Skin irritation
Other regional “collateral damage” (e.g., functional loss in salivary
glands, bowels, infertility, memory loss)
• More cancer
General Categories of Cancer Treatments:
Surgery
Radiation
Chemotherapy
Targeted therapy
Biologics
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Chemotherapy
What?
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• Chemicals given orally, IV, IM, IP, IT, topically—depending upon the drug
Chemotherapy
Why?
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• To eradicate/cure
• To control tumor growth
• To ease symptoms
Chemotherapy
How?
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Alkylating agents (directly damage DNA)
Anti-metabolites (interfere with biosynthesis reactions)
Agents that interfere with DNA replication
Agents that interfere with mitosis
Chemotherapy
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Chemotherapy
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Chemotherapy
agents that interfere with DNA replication
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Chemotherapy
agents that interfere with mitosis
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Chemotherapy
Downsides
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Fatigue
Nausea
Potential infection
Bleeding
Many other local/regional/systemic effects
More cancer
Develop resistance
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General Categories of Cancer Treatments:
Surgery
Radiation
Chemotherapy
Targeted therapy
Biologics
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Targeted Therapy
What?
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• Small molecules directed to intracellular messengers
• Antibodies directed to cell-surface molecules
 Antibody-dependent cellular death
 Complement-dependent cytotoxicity
 “Delivery” mechanisms
o Toxins or pro-toxin converting enzymes
o Radioactive isotopes
Targeted Therapy
Why?
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 To kill cancer cells Selectively and Specifically!
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Targeted Therapy
Downsides
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Often not orally-available (must be infused)
Expensive
Not many; few side effects
Develop resistance
General Categories of Cancer Treatments:
Surgery
Radiation
Chemotherapy
Targeted therapy
Biologics
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Biologic Therapy
Why?
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To inhibit cancer-benefitting biologic processes
To alleviate side effects of other therapies (e.g., depressed immunity, bleeding)
Biologic Therapy—
Anti-angiogenics
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Biologic Therapy—
Anti-metastasis drugs
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Biologic Therapy—
Other drug targets
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Differentiation promoters
Immune system stimulators
Epigenetic modifiers
Coagulation promoters
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Testing new treatments
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High throughput assay
• Effective at therapeutic doses
• No/minimal off-target effects
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http://www.cancer.gov/about-cancer/treatment/clinical-trials/search
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Phase I:
• Small numbers of subjects (~20)
• Subjects usually have advanced disease
• Purposes:
 gauging toxic effects (maximum tolerated dose) and
 pharmacokinetics (how long the drug “lasts”—concentration/time) in vivo
 pharmacodynamics (is drug at functional concentrations) ex vivo, often using a
surrogate marker
Goal is to generate
a "therapeutic
window"-dose that
is therapeutically
effective but below
the maximum
tolerated dose.
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Phase II:
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Larger numbers of subjects (typically <100)
Often low doses of drug (“bottom” of therapeutic window) tested
Specific patient population, may/may not have been previously treated
Goal is to observe clear signs of efficacy
Phase III:
• Even larger numbers of subjects (hundreds-thousands)
• Some subjects receive the study drug and others serve as controls
 Randomized
 Typically, control subjects receive current 'standard of care'
• Low bar for FDA approval because participants are already failing other treatments
• The drug only as to be better that ‘standard of care’ in only one aspect (e.g., fewer
side effects, weight gain, better at shrinking tumor)
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Phase IV:
• After FDA approval
• “Post-marketing surveillance”
• Goal is to:
 fine-tune the best patient population in which to use the drug (different type
of cancer, subtype of the original cancer type tested)
 to better define effective use in other ways (e.g., other similar uses)
 To assess long-term effectiveness/safety
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