Theory of cancer evolution (2)

Question 1

biomarker

Answer 1

= biological molecule - sign of disease/condition/abnormal process

Question 2

personal therapy

Answer 2

not only targeted to type of cancer,
patients own cancer information is used to guide therapy

Question 3

ideal clinical tool (5)

Answer 3

robust measure of tumour heterogeneity thats:
- rapid
- cost effective
- sampling minimally invasive
- comprehensive tumour smapling (no spatial baises)
- simple proxy biomarkers to assay ITH reliably

Question 4

tumour heterogeneity

Answer 4

differences between
- tumors of the same type in different patients,
- cancer cells within a single tumor,
- a primary (original) tumor and a secondary tumor.

Question 5

minimally invasive procedure eg.

Answer 5

liquid biopsy

Question 6

3 evolutionary therapy strategies

Answer 6

• targeting a clonal mutation
• targeting combined clonal mutations
• adaptive therapy

Question 7

targeting clonal mutation -

Answer 7

• targets specific clone
• expansion of other clone after therapy, due to loss of competition (& can become insensitive to therapeutic agent)

Question 8

targeting combined clonal mutations -
(+ a limitation of this)

Answer 8

• targets multiple clones …
• leads to remission
  (drugs may interact = really bad side effects, & patients unable to tolerate this treatment)

Question 9

adaptive therapy -

Answer 9

• target + bring down major clones
• monitor patients progression (with evolutionary biomarkers)
• if previously targeted clone declines too much then interrupt therapy
  so competitive clone can restrict growth of resistant clone

Question 10

TRACERx trials

Answer 10

translational research study aimed at transforming our understanding of cancer evolution

Question 11

therapy monitoring looks for …

Answer 11

ctDNA and CTCs shed from tumours (if therapy is killing cancer cells –> cellular/genomic material released from apoptotic bodies)

Question 12

how is chronic lymphocytic Leukemia clinically affectively managed ?

Answer 12

we know mutations in certain genes that lead to resistance,
~5 genes are screened for ~5 mutations (which occur in 99% of resistance cases)

Question 13

risk stratification

Answer 13

enables providers to identify the right level of care and services for distinct subgroups of patients

Question 14

understanding the timings of mutations across cancers allows you to determine if intervention is needed or not, how?

Answer 14

mutations can be used to determine between pre-malignant or early invasive lesions

Question 15

how large data & computational methods help with predicting tumour evolution ?

Answer 15

can classify patients on basis of how their tumour evolved
- this has implications for anticipation of disease progression

Question 16

key early mutagenic processes associated with tumours (2 e.g.’s)

Answer 16

1. Cancer with active APOBEC deaminase activity - treat cells to repeat this signature activity + to link it to a process associated with tumours ..)
2. C > T mutations, that occur with age (clock like mechanism)

Question 17

spontaneous deamination of 5-methylcytosine (5meC) causes …

Answer 17

C to T mutations

Question 18

barriers to translation of these cancer preventions …

Answer 18

• toxicity (in combination approaches)
• need understanding of complex mechanisms that lead to resistance (eg. fibroblasts protecting cancer cells)
• somatic cells with cancer mutations are not cancers
• predictability is limited, bc of cancer evolution