Pharm: Targeted Therapies Flashcards Preview

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Flashcards in Pharm: Targeted Therapies Deck (55)
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1
Q

The most common inherited breast cancer TSG mutation is what?

A

BRCA 1/2

2
Q

One cancer accelerated by a mutated c-kit oncogene is the ____ ____ tumor.

A

GI stromal tumor

3
Q

Mutations in ____ and ____ can lead to malignancies in a small percentage of lung cancers.

A

EGFR; ALK

4
Q

Usually, how many mutations are required to allow cells to overcome the body’s boundaries for cell growth?

A

multiple.

5
Q

What is the goal of genomic medicine in cancer therapy?

A

to identify mutations sites and treat specifically the problem with targeted therapy

6
Q

____ receptors are very important targets for patients with breast and prostate cancers.

A

Hormone

7
Q

What is c-Kit?

A

an oncogene that encodes a cell surface RTK that can activate the RAS and the PI3K pathways

8
Q

What type of cancer is c-Kit mutation associated with?

A

GI stromal tumor (GIST)

9
Q

What drug works well against c-Kit mutation tumors?

A

imatinib - because it turns off the tyrosine kinase, which mutated c-Kit is

10
Q

Adenocarcinoma of the lung often arises in non-smokers, especially in ____ countries.

A

East Asian

11
Q

Cetuximab blocks what receptor, and what cancer does this treat best?

A

EGFR (blocks externally); colon cancer

12
Q

Genes with mutations that are most amenable to treatment with drugs that inhibit EGFR are located where?

A

exxons 19 & 21 of the EGFR gene

13
Q

Erlotinib blocks what receptor, and what cancer does this treat best?

A

EGFR kinase (blocks internally); lung cancer

14
Q

An adenocarcinoma of the lung is found to have an ALK mutation. What drug will be therapeutic for this cancer?

A

Crizotinib

15
Q

What is the most common cause of tonsillar cancer in non-smokers?

A

HPV infection - common cause of oropharyngeal cancer

16
Q

In head and neck cancer due to EGFR mutation, EGFR can be inhibited by the drug ____, which inhibits the receptor from the ____ side.

A

Cetuximab; externally

17
Q

4 goals of treatment, according to Dr. Weir:

A
  1. cure disease
  2. extend life
  3. better quality of life
  4. prevent impending disaster
18
Q

What is the most common brain neoplasm and from what cells does it derive?

A

Glioma; glial cells

19
Q

What is the grading scale for glioma severity?

A

Grades 1-2 considered benign; Grades 3-4 considered malignant; Grade 4 is a glioblastoma

20
Q

A recurrent glioblastoma would most likely respond to targeted therapy with what drug?

A

bevacizumab

21
Q

Bevacizumab is useful therapy for what type of cancer?

A

glioblastoma - VEGF inhibition

22
Q

Cetuximab is useful therapy for what type of cancer?

A

colon cancer, H&N cancer, lung cancer - EGFR inhibition

23
Q

Crizotinib is useful therapy for what type of cancer?

A

lung cancer - EML4-ALK inhibition

24
Q

Erlotinib is useful therapy for what type of cancer?

A

lung cancer - good for EGFR mutation in adenocarcinoma

25
Q

Imatinib is useful therapy for what type of cancer?

A

CML - BCR-ABL mutation

GIST - c-Kit mutation

26
Q

Glioblastomas produce a lot of ____ for promoting angiogenesis.

A

VEGF

27
Q

What is the MOA of bevacizumab?

A

binds VEGF-A and prevents it from binding the VEGF-2 receptor; thereby preventing the Ras and PI3K pathways

28
Q

What does bevacizumab achieve clinically?

A

takes away the glioma side effects by taking away the blood supply and reduces the swelling that’s putting pressure on other brain areas and producing symptoms

29
Q

What is a common cause of iron deficiency anemia, and how could it also be due to cancer?

A

to lose iron is to lose blood! so a common cause is GI tract bleeding; could also be renal cancer causing blood to be lost slowly in urine

30
Q

Renal cell carcinoma and glioblastomas are particularly dependent on ____, providing a target for anti-cancer therapy.

A

angiogenesis

31
Q

Von Hippel Lindau syndrome comes from a mutation in ____ (gene) which encodes ____ (protein).

A

TSG; hypoxia inducible factor (HIF)

32
Q

Most clear cell carcinomas of the kidney have a mutation in what gene?

A

von Hippel Lindau

33
Q

Mutation of von Hippel Lindau results in lost inhibition of ____, which drives production of what and results in what?

A

HIF, which drives production of VEGF which stimulates angiogenesis allowing for tumor growth and expansion

34
Q

What is the MOA of sunitinib, and what cancers is it good at treating?

A

inhibits angiogenesis by blocking VEGFR tyrosine kinase activity intracellularly, and preventing the RAS and PI3K pathways from inducing angiogenesis; makes it good at treating renal cancer

35
Q

Breast cancers that are both estrogen and progesterone receptor positive means what?

A

it means that the cancer is in part driven by estrogen and progesterone

36
Q

Where is the estrogen receptor located?

A

intracellularly; it’s a hormone receptor

37
Q

True or false: there is cross-talk between the estrogen/estrogen receptor and the GFR/mTOR pathway.

A

True

38
Q

What is the MOA of tamoxifen and what cancer is it best at treating?

A

blocks estrogen receptors and hormone response of breast cancers

39
Q

What is another good drug for treating estrogen receptor-positive breast cancers and in what population is this drug useful (and why)?

A

aromatase inhibitors–block formation of estrogen; only useful in post-menopausal women because estrogen production will be increased to overcome the inhibition

40
Q

What drug is used to block mTOR? Blocking mTOR in addition to estrogen receptors will have what effect on breast cancer?

A

Everolimus; together with estrogen receptor inhibitor (tamoxifen) it will decrease the time to cancer progression

41
Q

What is the HER receptor family?

A

TM receptor tyrosine kinase that binds GFs, implicated in breast cancers

42
Q

What is the MOA of Trastuzumab and what cancer does it work best on?

A

externally blocks HER-2 receptor; works best on breast cancer recurrence and metastasis

43
Q

What other drugs combine well with Trastuzumab?

A

hertuzimab - another HER inhibitor; also combines with DM-1 a chemotherapy that is only brought into a breast cancer cell

44
Q

What drug would prostate cancer respond best to?

A

enzalutamide

45
Q

How does testosterone interact with the androgen receptor?

A

testosterone enters the cell, is converted to DHT; DHT binds the cytoplasmic androgen receptor and associates with AR; then transmigrates to nucleus to transcribe genes

46
Q

What does the LHRH agonist and antagonist do?

A

blocks testosterone production; but the agonist will first release a lot of LHRH, so requires simultaneous androgen receptor inhibition

47
Q

What is the MOA of enzalutamide and what cancer does it best treat?

A

it binds and blocks androgen receptor, prevents its migration into the nucleus, and blocks action within the nucleus; treats prostate cancer

48
Q

What does castrate resistant prostate cancer mean?

A

it means it is progressing despite markedly reduced testosterone levels

49
Q

What cancer is the B-Raf mutation associated with?

A

melanoma

50
Q

Melanoma that develops from sunburn in youth is associated with mutation in what gene?

A

B-Raf V600

51
Q

What pathway is B-Raf involved in?

A

B-Raf –> Mek –> ERK –| BIM –> Bcl-2/XL –> survival

*So if B-Raf is mutated and fails to produced ERK, BIM won’t be inhibited and the cell will survive

52
Q

What pathway is PTEN involved in?

A

PTEN –| PI3K –> AKT –> BAD –| BAD/BAX –> BCL-2/XL –> survival
*So if PTEN is mutated and fails to inhibit PI3K, BAD won’t be inhibited and the cell will survive

53
Q

What is the MOA of vemurafenib and what cancer is it good at treating?

A

inhibits the mutated BRAF V600E/K, preventing cancer cell survival; good for melanoma

54
Q

A germline mutation in PTCH will lead to what syndrome, which is a condition involving defects of multiple body systems and a predisposition to what carcinomas?

A

Gorlin syndrome; basal cell carcinomas

55
Q

What is the MOA of vismodegib and what cancer is it useful in?

A

blocks SMO in the the Hedgehog pathway therby preventing tumors; useful in basal cell carcinoma