Skin Cancer Pharm Flashcards
(46 cards)
What are some common sites of metastasis of skin cancer?
intestines, lung and brain
What are the drugs for basal cell carcinomas?
- Aminolevulinic Acid
- Porfimer
- Sonidegib
- Vismodegib
What are BCCs typically caused by?
They are usually caused by a combination of cumulative and intense, occasional sun exposure.
Are BCCs likely to metastasize?
BCC almost never spreads (metastasizes) beyond the original tumor site. Only in exceedingly rare cases can it spread to other parts of the body and become life-threatening.
It shouldn’t be taken lightly, though: it can be disfiguring if not treated promptly.
What are the treatment options for BCCs?
- surgical excision (Mohs surgery has the best cure rate)
- cryotherapy
- radiation
- photodynamic therapy (aminolevulinic acid)
- targeted therapy (for advanced BCCs)
What is a common signaling mutation in BCCs?
Hedgehog signaling, an important pathway in embryogenesis and organ maturation but one that is typically quiescent by adulthood except for minor tissue maintenance, but can also become dysregulated in some forms of cancer, including BCC.
Hedgehog mutations have also been implicated in what kinds of cancers?
- rhabdomyosarcomas
- medulloblastomas
What are some of the pathological consequences of upregulated HH signaling?
-upregulation of anti-apoptotic protein Bcl-2, induction of VEGF and angiogenesis
How do drugs attack abnormal HH signaling?
They (Vismodegib/Sonidegib) must act at or below the level of the transmembrane protein SMO (smoothened) because the pathway is ligand independent, so blocking HH binding to PTCH1 (protein patched homolog 1) is ineffective
What are the AEs of Vismodegib and Sonidegib
- Teratogenic female AND male (makes sense since HH is invovled in organ formation)- up to 20 months after use in women and 8 months in semen in men
- alopecia
- endocrine dysfunction
- GI toxicity
- elevated serum creatinine
What drugs are available for squamous cell carcinoma?
- aminolevulinic acid
- afatinib
- Cetuximab
What are squamous cell carcinomas?
“Squamous cell carcinoma (SCC) is an uncontrolled growth of abnormal cells arising in the squamous cells, which compose most of the skin’s upper layers (the epidermis). SCCs often look like scaly red patches, open sores, elevated growths with a central depression, or warts; they may crust or bleed. They can become disfiguring and sometimes deadly if allowed to grow.
What are the treatment options for SSCs?
- surgery
- photodynamic therapy (aminolevulinic acid)
- targeted (afatinib and Cetuximab)
- conventional drugs (bleomycin, docetaxel, hydroxyurea, fluorouracil
What is Afatinib? Cetuximab?
PO irreversible TKI for EGFR and HER2
Cetuximab- EGFR monoclonal bloking phosphorylation and activation of kinases
Toxicities of targeted drugs?
These drugs can affect virtually any organ in the body due to their chronic use resulting in accumulation. Make sure to monitor closely
What are the major toxicities of EGFR ddrugs?
- derm rxns especially common (rash, dry skin, etc.)
- GI toxicity
- rarely CV toxicity
What are the drug options of actinic keratosis?
- Diclofenac
- Imiquimod
- Ingenol Mebutate
- Aminolevulinic acid
- Methylaminolevulinic acid
What is actinic keratosis?
Actinic keratosis, also known as a solar keratosis, is a scaly or crusty growth (lesion) that most often appears on areas of the body commonly affected by the sun. You’ll often see the plural, “keratoses,” because there is seldom just one. In the beginning, actinic keratoses are frequently so small that they are recognized by touch rather than sight. It feels as if you were running a finger over sandpaper. Patients may have many times more invisible (subclinical) lesions than those appearing on the surface.
What is the typical progression of actinic keratoses?
Most often, actinic keratoses develop slowly and reach a size from an eighth to a quarter of an inch. Early on, they may disappear only to reappear later. Most become red, but some will be light or dark tan, pink, red, a combination of these, or the same color as your skin. Occasionally they itch or produce a pricking or tender sensation. They can also become inflamed and surrounded by redness. In rare instances, actinic keratoses can even bleed.”
If left untreated actinic keratoses can transform into what?
SCC
Treatment options for actinic keratoses?
- cyrosurgery is most common
- topical options (5-FU creams such as imiquimod creams and ingenol mebutate)
How does Imiquimod (Aldara) work?
It is an immunostimulant that primarily affects Toll-like receptors (and maybe adenosine receptors) to increase immune responses
AEs of Imiquimod?
- topical site irritation (avoid sunlight)
- can compromise condom and diaphragm integrity when used to treat genital warts
How does Ingenol Mebate work?
The drug produces an interesting biphasic effect. Rapid lesion necrosis begins 1 to 2 hours after application. Specific neutrophil mediated antibody (Ab)-dependent cellular cytotoxicity (ADCC ) follows within several days of drug application. Recall that, in neutrophil-mediated ADCC, Ab are produced by B cells and bind to specific antigens on dysplastic epidermal cells. These Ab also bind to receptors on infiltrating neutrophils. Occupation of receptors on neutrophils by specific Ab triggers neutrophils’ killing mechanisms, including release of cytotoxic agents such as ROS, which destroy dysplastic epidermal cells.
