Chemo Sensitivity test

intheclub

Hi, I’m in NZ - stage 4 lobular snd looking at the tests that tell you what chemo will work.

I’ve done Foundation One which my oncologist recommended.

I’ve just found out about the Geonostics Exacta Test - snd the Gradient test I’m confused so just wondering if anyone knows what the differences are - or which one is best. Xox

nnguyen

Hello,

I don’t see the Gradient test listed on Geonostics site. I believe the Exacta test is Geonostics most comprehensive tumor analysis. The Exacta test generates quite a bit more information than the Foundation1Cdx test. Some of the key differences are.

• Exacta looks at more genes
• It does RNA sequencing
• Assume it uses both tissue biopsy and liquid (blood) biopsy per test
• All above allows drug (chemo, targeted, etc) efficacy testing, and toxicity risk.
• List drugs that might work including using off-label (intended to use for other indications) drug. It also list non-pharmaceutical substances that might have some efficacy.

RNA sequencing is quite important in that it enables pathways (connections between inter/intra cell’s machinery) and signaling (when to do what) analysis to determine how tumor cells proliferate, which would lead to which drug might work. RNA sequencing also allow the quantification (how much) of protein express. Without RNA sequencing, assay like FISH or IHC would be needed to determine protein overexpression. FISH determines the number of copies of a gene. IHC directly determines amount of protein.

Incidentally, these phrases overexpression, amplification, and mutation do not mean the same thing. For example Her2 positive in the context of cancer means over expression of Her2 protein, i.e produce more than “expected” Her2 protein (her2 receptor). Her2 amplification more than the “expected” number of Her2 genes, which usually leads to over expression of Her2 protein. Her2 mutation is a change in DNA sequence for that gene. This could lead to resistance to drugs that target Her2. Her2 over-expression could be from having more than expected number of Her2 gene. One could also have “normal” number of Her2 gene but still have overexpression of Her2 protein due to faulty in the signaling process that activates those genes more often.

With respect to drug testing (used to be called CCDRT cell culture drug testing), existing data seems to point to it is more accurate in predicting resistance vs efficacy. Intuitively, live original cancer tissue (cells) would provide more accurate result than culture tumor cell. Inaccuracy resulted from cultured cells could be due to genetic drift from elapsed time, repetition, selection pressure of culture medium (vs body). Other inaccuracy could be due to signaling induces by environment external to the cells. Some drug would be metabolized by the liver (and elsewhere) before getting to the cells. Drug with an immune based component would be harder to test since immune cells around the cancer cells being tested need to be there.

Still there are companies that claim they have overcome these issues. I would use these drug tests when there is no (or few) options left, or when there are lots of options. Especially if there are tumor cells in liquid biopsy, I would want to increase the chance of neutralizing them, since they’re the one likely establish new metastatic site. I would want to understand (or have someone explain to me) to the lowest level (per current knowledge) biological detail why/how the test result is valid.

Probably more than what you guys want to know. Please correct any inaccurate info above.