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Biomarkers for treatment efficacy evaluation


asafsh
(@asafsh)
Joined: 2 years ago
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I am trying to find appropriate biomarkers for mesenchymal chondrosarcoma complementary treatment efficacy evaluation.

When looking at blood analysis figures i noticed increased LDH level before the next chemo cycle. Guess this value could be used for current treatment protocol. 

What else is worth looking at for this pathology?


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Daniel
(@daniel)
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Hi Asafsh,

 

In general if there is no marker you can use, you can indeed use LDH and a few others such as K, uric acid, liver profile. Depending on the dynamics of one or more of these you can guess what happens. Regarding LDH, if its a fast jump up and down, typically is the effectiveness of the treatment. If its a constant move up, it can represent evolution, if constant move down, tumour reduction. Of course things are more complex than this, but this could be a good starting point to observe.  Note: not all cancers lead to impact on LDH.

 

Kind regards,

Daniel

 

 

 


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asafsh
(@asafsh)
Joined: 2 years ago
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Hi Daniel 

Thanks for taking time and answering question. 

Is it feasible to add kidney function eGFR as well?

I had a look to LDH values and those are jumping (LDH values taken right before chemo):

2020.01.26: 302
2020.02.23: 367
2020.03.22: 269 <- tumor size is almost the same as before first chemo start.
2020.06.14: 334 <- tumor size and pain are increased.

From last MR - tumor is increased. May be i am wrong but it seems that metabolism is changing and tumor is switching to gluconeogenesis (accompanied by cachexia).

Unfortunately, MD didn't ask to measure blood glucose, so i couldn't check it from history. 

Best Regards


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johan
(@j)
Joined: 3 years ago
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@asafsh

Hi, have you looked at Honokiol?

https://pubmed.ncbi.nlm.nih.gov/19880244/

"Honokiol Induces Cell Apoptosis in Human Chondrosarcoma Cells"

Also, in this study "After HNK treatment, the cardiac contractile ability increased and the LDH activity decreased"

https://www.researchgate.net/publication/326486731_Honokiol_Protects_against_Anti-_b_1-Adrenergic_Receptor_Autoantibody-Induced_Myocardial_Dysfunction_via_Activation_of_Autophagy

 


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asafsh
(@asafsh)
Joined: 2 years ago
Posts: 82
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@johan

Dear Johan, thank you for your suggestion. I had to administer it 2 months ago but couldn't due to disrupted supply chain because of covid. 

right now options are limited as current chemo had been interrupted after second day of 3 day regimen due to increased tumor pressure on brain.

So i have to find hummer to shrink the tumor before next chemo can be done to avoid same complication again and prepare patient for proton therapy traveling. I am afraid of palliative neurosurgery because of patient's weak condition.

Pazopanib, imatinib, rapamycin, trabectedin, and metronomic chemotherapy are on my list. Together with redo.

 


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Daniel
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@asafsh

Hi Asafsh,

Indeed that is whats happening when LDH goes up (increased fermentation, increased blood glucose levels, etc.). This is the moment when I would push more on the anti-inflammatory supplements and drugs, and gluconeogenesis inhibitors.

Low dose immunotherapy is also an option. Here is a PhD thesis on Chondrosarcoma and immunotherapy https://tel.archives-ouvertes.fr/tel-01394381/file/TH2016SIMARDFRANCOIS.pdf

Adding Plorizin to low dose chemo could also make a big difference https://www.cancertreatmentsresearch.com/phlorizinphloretin-a-strong-glucose-transport-inhibitor/

Have you considered modulating the thyroid hormones? https://www.cancertreatmentsresearch.com/induced-hypothiroidism-hypothyroxinemia/

Have you tried DMSO in combination with Honokiol or others to apply locally?

You could also check the response to DCA locally and if it works use it systemically.

Kind regards,
Daniel


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asafsh
(@asafsh)
Joined: 2 years ago
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@daniel

Dear Daniel. Thank you for your opinions. 

I had seen this thesis and researched few options from there as:

- BCL inhibition with plant supplements didn't give suitable results. May be i didn't achieve required objective, but it seems that most of the BCL family needs to be suppressed, which is not achievable efficiently with supplements. From drug point of view - Venetoclax suppress only BCL-2 member of BCL family which is not enough to stop tumor proliferation. Navetoclax which suppress more than one BCL member is quite toxic and wasn't approved (still experimental drug).

- PDL1 inhibitor isn't suitable there is no such expression found in genetic tests from biopsy.

- MTORC is a valid option. The most potent is the dual inhibitor of MTORC1 and MTORC2 Sapanisertib which is not approved yet (on trials). Available - rapamycine first generation mtorc inhibitor. Also combination of imatinib-rapamycin-ciprofloxacine-interferone-alpha was proposed as a treatment (no one tried them yet though). 

- Anti-angiogenic - pazopanib is used alone or with rapamycin (pazolimus). Latter combination showed some efficacy in high grade sarcoma (from Israel study and case report on mesench chondro)

- Hedgehog inhibitor Mebendazole isn't efficient enough to rely only on it. Didn't use more serious drugs from this family, though.

- plorizin and DCA is out of reach and it will take 1 month to obtain. 

- tried to get help on thyroid hormone and found no doctor willing to assist me. Same is with bisphosponates. 

- HDAC inhibitor didn't show enough efficacy alone. May be combination with others may help. but no time to try.

I would like to try DCA and plorizin but it needs time to obtain them. Can't do administration of more serious drugs myself - nervous of possible mistake with such tools.

 

Best Regards

Asaf


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Daniel
(@daniel)
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HI Asaf,

You are welcome. I understand.

- PD/PDL1 inhibitors can work even when expression is not found

- Hedgehog inhibitor - there are others to try indeed

- plorizin and DCA - there were some people in Turkey using therm - at least DCA should be very easy to get unless you have challenges at the border - but it should not be with DCA

- hmm ... its a pity you do not find a doc to help with thyroid hormones and bisphosponates - this should be easy ones to get support with ...

Maybe you can test topical application in some small areas of the tumor?

Is it now possible to travel? You could go to the clinic in Romania - it should not be that far from you. And not so expensive.

Kind regards,
Daniel

 


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Daniel
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@asafsh 

Btw, this should be easy to implement and accessible https://www.cancertreatmentsresearch.com/mistletoe-viscum-album-l/


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asafsh
(@asafsh)
Joined: 2 years ago
Posts: 82
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@daniel

Hi Daniel

Thank you, appreciate for your help!

- PD/PDL1 should be assessed and administered by knowledgeable MD and i guess in combination with other drugs. I can't find MD. Latest MD Professor, started palliative IE chemo for 6 cycles even after i brought to him all papers found for the subject. Here they don't want to try new things and stick to the protocol comfort area. 

- Hedgehog inhibitors are serious drug same reason as above. 

- plorizin and DCA are used here in at least one clinic but they turned me out once heard about pathology. They choose patients unfortunately. 

- Yes, it is hard to find here real doctors who are not afraid of doing something new and willing to study the subject.

- I am OK with subcutaneous part of tumor as far as it is not increasing too much. The one which is in brain i get nervous about. Patient was moved to the intensive care after tumor expressed pressure on brain. Though i also suspect med personal for not following patient properly during chemo (that chemo is a bit hard VIDE protocol and put a lot of stress on body). 

- Patient need to renew her passport before going abroad and that will take a time (few weeks). Also, good to have proton or ion carbon therapy (which is most efficient on sarcomas) around with neurosurgery if it will be needed. Stereotactic radiotherapy will be less efficient in chondrosarcoma. So multidisciplinary center is a must. 

I may also add bevacizumab just to win a time before main treatment will be started though i don't know whether its efficacy will be compromised because of bevacizumab + docetaxel application:

Efficacy of Weekly Docetaxel and Bevacizumab in Mesenchymal Chondrosarcoma: A New Theranostic Method Combining Xenografted Biopsies With a Mathematical Model

 

Best Regards

Asaf


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johan
(@j)
Joined: 3 years ago
Posts: 592
 

Hi Asaf,

have you considered NAMPT inhibitors?

https://mcr.aacrjournals.org/content/15/12/1714


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asafsh
(@asafsh)
Joined: 2 years ago
Posts: 82
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@daniel

Thank you!

The chemo is interrupted in the middle and i am afraid that i need to gain time before next cycle, otherwise patient will run into serious problem. mistletoe can be used after tumor will be shrunk a bit. 


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