Hi,
I have the EFGR mutation and about to start 4 cycles of chemo (Cistaplin+Vino) followed by Tagrisso tablets.
I am wondering about the above. I mentioned this to my oncologist at our first meeting last Wednesday, but she didnt provide an answer. I have asked a follow up question as to whether I am showing this inhibition. If I am not, I have pointed her to the third article, which seems to point to a treatment by KTZ+Dex.
Below are extracts from a 2011 and 2018 articles. I have read these and a few others like it. But as I have reached the limit of my understanding and can find no others from when I first searched some months ago - when first diagnosed. I was wondering if anyone has come across this in their treatment ?
Many thanks and Best Wishes,
Chas.
a) In summary, we correlate CYP24A1 mRNA expression with survival in resected lung AC. Our data demonstrate that overexpression of CYP24A1 mRNA is associated with poorer survival of lung AC patients and an inverse relationship between CYP24A1 mRNA expression and differentiation status of the lung cancer. Increased CYP24A1 mRNA counteracts the antiproliferative effect of 1,25-D3 in lung AC cancer cell lines, suggesting that high CYP24A1 mRNA expression in NSCLC leads to abrogation of antiproliferative effects of 1,25-D3 and ultimately poorer survival. CYP24A1 is not only a prognostic biomarker for lung AC but tumor levels may allow individualized secondary prevention strategies using either 1,25-D3 alone or in combination with a CYP24A1 inhibitor. Further studies assessing pulmonary vitamin D metabolism in lung AC are underway in our laboratory.
b) Vitamin D metabolites exhibit chemopreventive, antiproliferative, and antimetastatic activity in preclinical models of lung cancer. Besides having direct actions on tumor cells, vitamin D may control lung cancer by favorably altering the lung tumor microenvironment and immune function. Several factors are likely to modulate vitamin D activity in lung cancer patients including active cigarette smoke exposure, somatic variation in vitamin D pathway genes, and molecular heterogeneity of lung tumors. Promising data exist regarding vitamin D actions in individuals who have chronic obstructive pulmonary disease and are at elevated risk for lung cancer. However, vitamin D-containing therapies have yet to demonstrate significant activity in unselected, advanced lung cancer patients. Future trials may benefit from a personalized medicine approach wherein the molecular profile of a patient's lung tumor and a patient's vitamin D status are used to identify individuals who are more likely to benefit from vitamin D supplementation.
c) In summary, our data demonstrate in vitro and in vivo inhibition of CYP24A1 activity by KTZ. The inhibition of CYP24A1 activity by KTZ is associated with increases in systemic calcitriol exposure, together with the activation of AIF-induced apoptotic pathway by a combination of calcitriol + KTZ + Dex, contributes to the enhancement of calcitriol antitumor effects in preclinical models.
Hi Chas, sorry you haven’t had a reply to your post. I have searched the site and cannot find any other discussions regarding this. There is a lot of information out there on Google, but a lot of is regarding research, trials etc and much of it isn’t in the UK.
I tend not to Google, as I know I will drive myself mad with all the information. I just trust my sarcoma oncologist to know what is best for me and treat me accordingly, after all she’s the expert. x
