targeted cancer therapies Flashcards
her 2 neu
1) found in 25-30% of breast cancers
- likely hood of metastasis goes up with decreased survival
2) human epidermal GF receptor 2
herceptin
1) method to block growth of cancer cells
- monoclonal antibodies that attach to specific protein to halt growth
2) HER2 specific trastuzamab (herceptin)
chemotherapy
1) alkylators
2) antibiotics
3) antimetabolites
4) topoisomerases
5) mitosis inhibitors
hormonal therapy
1) steroids
2) anti-estrogens and androgens
3) LH-RH analogs
4) anti-aromatases
immunotherapy
1) interferon
2) interleukin 2
3) vaccines
new classification based on target
1) tumor: DNA (non-specific mostly), RNA, proteins (super specific)
2) endothelium: DNA and proteins
3) ECM
4) immune system
5) host cells
bisphosphonates
1) inhibit osteoclasts and affects bone remodeling
2) dental infections are bad
cross linking agents
1) cytotoxic drugs / alkylating
2) DNA strands are bound, preventing transcription
- DNA break
3) platinum based therapies are commonly used
- cisplatin, carboplatin
- others include cyclophosphamide, doxirubacin
4) antimetabolites
- interfere with production and maintenance of DNA
- methotrexate
antihormones
1) estrogen receptors
- tamoxifen and fulvestrant
- lots of breast cancers have these
2) androgen receptors
- prostate cancer and some salivary gland cancers
- flutamide, biclutamide
targeted cancer therapy
1) monoclonal antibodies
- attach antigens on the surface, altering cell signal
- all end in -mab
- admin by injection
- about 20,000 atoms (large)
2) small molecules
- target intracellular signaling protein
- inhibitors
- end in -ib
- easily produced and taken orally
if transducing signals do not occur
1) cells cannot divide
breast cancer
1) her2 overexpressed on surface of 30% breast cancer tumors
- benefit from drugs that target it
- trastuzamab: inhibit signal
colon cancer
1) 20% have kras oncogene (mutated)
- affects EGFR signal transduction, and mutated one is continuously active
- cetuximab is a potent anti EGFR antibody
- patients with normal KRAS respond better to treatment by mAbs
lung cancer
1) 2 genes fuse to form a new gene in 5%
- functional protein EML4-ALK which induces malignant cell formation
- crizotinib targets this rearrangement
melanoma
1) BRAF mutation in 60%
- MAPK pathway activation
- vemurafenib
head and neck cancer
1) oral cavity squamous cell carcinoma
- EGFR inhibits are used routinely to improve survival in some cases, not 100% effective
2) salivary gland malignancies
- have been shown to express HER2
side effects of monoclonal antibody therapy
1) myelosuppression
- renders the patients pancytopenic
- prone to infection, bleeding and anemia
vascular endothelial GFs
1) tyrosine kinases (on off switch to many cellular functions)
2) inhibitors prevent tumors by preventing vascular proliferation
3) also affect tissue response to injury and related to osteonecrosis of the jaw (lack of blood is bad for this)
side effects of patient on meds
1) stomatitis
2) dry mouth
3) pain
4) dysgeusia
5) gingival bleeding
jaw osteonecrosis
long time complication of radiotherapy
2) IV bisphosphonates (osteoclast inhibitor)
3 )denosumab targets RANKL
4) angiogenesis inhibitors VEGF
5) risk of MRONJ!!!!
- IV bisphosphonate 1%
- if all above is combined with VEGF, 10%
impaired wound healing
1) agents that inhibit VEGF
- impair wound healing
- compromised wound strength
- affect vascular nourishment and reepithelialization
2) consider if surgery is really necessary
- drug holiday depending on holiday
susceptibility to infections
1) some targeted therapies can cause candidiasis etc
dry mouth
1) receiving chemo
2) tyrosine kinase inhibitors (high freq)
3) lower freq in people on mAbs
proposed treatment for stomatitis and mucositis
1 )erythema
- steroids
2) ulcers
- steroids
antibody therapy in the treatment of autoimmune diseases
1) theoretically, alternative to corticosteroids or cytotoxic drugs
2) possible to target each step in immune process, including cells expressing a specific autoantigen (increases risk of serious infection)
bisphosphonates effect of ortho
1) pyrophosphate analogues inhibit bone resorption
2) use of bisphosphonates does not contraindicate ortho
3) but, duration may be increased due to inhibition of osteoclasts
