targeted cancer therapies

Question 1

her 2 neu

Answer 1

1) found in 25-30% of breast cancers
- likely hood of metastasis goes up with decreased survival
2) human epidermal GF receptor 2

Question 2

herceptin

Answer 2

1) method to block growth of cancer cells
- monoclonal antibodies that attach to specific protein to halt growth
2) HER2 specific trastuzamab (herceptin)

Question 3

chemotherapy

Answer 3

1) alkylators
2) antibiotics
3) antimetabolites
4) topoisomerases
5) mitosis inhibitors

Question 4

hormonal therapy

Answer 4

1) steroids
2) anti-estrogens and androgens
3) LH-RH analogs
4) anti-aromatases

Question 5

immunotherapy

Answer 5

1) interferon
2) interleukin 2
3) vaccines

Question 6

new classification based on target

Answer 6

1) tumor: DNA (non-specific mostly), RNA, proteins (super specific)
2) endothelium: DNA and proteins
3) ECM
4) immune system
5) host cells

Question 7

bisphosphonates

Answer 7

1) inhibit osteoclasts and affects bone remodeling
2) dental infections are bad

Question 8

cross linking agents

Answer 8

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

Question 9

antihormones

Answer 9

1) estrogen receptors
- tamoxifen and fulvestrant
- lots of breast cancers have these
2) androgen receptors
- prostate cancer and some salivary gland cancers
- flutamide, biclutamide

Question 10

targeted cancer therapy

Answer 10

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

Question 11

if transducing signals do not occur

Answer 11

1) cells cannot divide

Question 12

breast cancer

Answer 12

1) her2 overexpressed on surface of 30% breast cancer tumors
- benefit from drugs that target it
- trastuzamab: inhibit signal

Question 13

colon cancer

Answer 13

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

Question 14

lung cancer

Answer 14

1) 2 genes fuse to form a new gene in 5%
- functional protein EML4-ALK which induces malignant cell formation
- crizotinib targets this rearrangement

Question 15

melanoma

Answer 15

1) BRAF mutation in 60%
- MAPK pathway activation
- vemurafenib

Question 16

head and neck cancer

Answer 16

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

Question 17

side effects of monoclonal antibody therapy

Answer 17

1) myelosuppression
- renders the patients pancytopenic
- prone to infection, bleeding and anemia

Question 18

vascular endothelial GFs

Answer 18

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)

Question 19

side effects of patient on meds

Answer 19

1) stomatitis
2) dry mouth
3) pain
4) dysgeusia
5) gingival bleeding

Question 20

jaw osteonecrosis

Answer 20

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%

Question 21

impaired wound healing

Answer 21

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

Question 22

susceptibility to infections

Answer 22

1) some targeted therapies can cause candidiasis etc

Question 23

dry mouth

Answer 23

1) receiving chemo
2) tyrosine kinase inhibitors (high freq)
3) lower freq in people on mAbs

Question 24

proposed treatment for stomatitis and mucositis

Answer 24

1 )erythema
- steroids
2) ulcers
- steroids

Question 25

antibody therapy in the treatment of autoimmune diseases

Answer 25

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)

Question 26

bisphosphonates effect of ortho

Answer 26

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