Genetic test result(TP53 variant)

[jeetu_g27]

Dear all ,

I just got genetic report of my father which is showing a variant TP53 p.lle195Phe .

Are there any specific agents to target this mutation ?

He is currently paralyzed below waist and is on chemo cabazitaxel 35 mg , completed 5 infusion till date . Below is his PSA summary after starting chemo

02 Nov 24 : 40.62

19 Nov 24 : 38.38

23 Dec 24 : 22

12 Jan-25 : 19.3

04 Feb 25 : 18.3

The PSA is becoming slightly stagnant , is this indicates that cancer cells are becoming resistive to cabazitaxel ?

[God_Loves_Me]

may be

cancer.gov/news-events/canc...

[NanoMRI]

Upon further investigations - imaging and biopsy, my TP53 turned out to be metastatic melanoma. Certainly not suggesting this for your dad - simply sharing what it is for me.

[jeetu_g27 in reply to NanoMRI]

Thanks for you inputs 🙏

[j-o-h-n]

Variant TP53 p.lle195Phe, Are there any specific agents to target this mutation ?

A I - ChatGPT said:

The TP53 p.Ile195Phe (I195F) mutation occurs in the DNA-binding domain of the TP53 tumor suppressor protein, which plays a crucial role in cell cycle regulation, apoptosis, and genomic stability. Mutations in TP53 are commonly associated with various cancers and often lead to loss of function or dominant-negative effects.

Targeting TP53 p.Ile195Phe Mutation

Currently, there are no FDA-approved targeted therapies specifically for TP53 p.Ile195Phe, but several approaches are being investigated:

1. Reactivation of Mutant p53

APR-246 (Eprenetapopt): A small molecule that restores the wild-type conformation and function of mutant p53. It has shown promise in TP53-mutated cancers, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).

COTI-2: A small molecule that stabilizes mutant p53 and enhances its tumor-suppressing activity.

2. Synthetic Lethality Approaches

PARP Inhibitors (e.g., Olaparib, Rucaparib, Talazoparib): These drugs exploit the defective DNA repair mechanisms in TP53-mutant cancers, especially in combination with other agents.

ATR/CHK1 Inhibitors: Targeting the ATR/CHK1 DNA damage response pathway is being explored in TP53-mutant cancers.

3. Immunotherapy Approaches

Immune Checkpoint Inhibitors (e.g., Pembrolizumab, Nivolumab): Some TP53-mutant tumors, particularly in lung and head & neck cancers, may respond better to PD-1/PD-L1 inhibitors.

p53-targeted Vaccines: Experimental vaccines aiming to elicit immune responses against TP53-mutant cancer cells.

What Next?

The specific impact of p.Ile195Phe on TP53 function is not fully characterized, so functional assays or genomic analyses may be needed.

Clinical trials may offer targeted therapies for TP53-mutant cancers. Checking databases like clinicaltrials.gov can help identify ongoing studies.

Would you like assistance in finding clinical trials for this mutation?

Good Luck, Good Health and Good Humor.

j-o-h-n

[jeetu_g27 in reply to j-o-h-n]

Thanks J-o-h-n🙏