In the deep-ocean of oncology, we bite through data to iluminate evidence. Ars medica in observatione consistir (Hipocrates)
Joined November 2025
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Today.
📄 Acquired resistance to the RAS(ON) multi-selective inhibitor daraxonrasib…
Nayak et al. | Nature Medicine | 2026
nature.com/articles/s41591-0…
168 pts treated → 100 developed acquired resistance → 57 had paired evaluable ctDNA → 44 at 160–300 mg. 🧵
Paired ctDNA (pretreatment vs progression) was analyzed with an 800+ gene panel.
Putative genomic resistance mechanisms emerged in 26/44 (59%).
Most striking:
→ KRAS amplification: 16/44 (36%)
→ MAPK/RTK/PI3K alterations
→ No secondary KRAS resistance mutations detected
43/100 patients had no evaluable ctDNA → caution.
Conclusion: Resistance mainly driven by amplification, with no secondary KRAS mutations.
Hypothesis:
→ Intensified RAS blockade (daraxonrasib + zoldonrasib)
→ RTK-directed combinations (amivantamab/T-DXd
@Nature
Can transcriptomics guide adjuvant treatment selection in resected pancreatic cancer?
Two recent studies suggest that transcriptomic profiling may help identify which treatment suits better.
@RemyNicolle @NelsonDusetti
Patients whose treatment matched the Pancreas-View prediction achieved dramatically longer DFS:
📈 50.1 months (mFOLFIRINOX)
📈 33.7 months (gemcitabine)
vs ~10 months in unmatched patients.
Neither GemPred nor Pancreas-View is ready for routine clinical practic (require prospective validation)
- Selecting adjuvant chemotherapy based on tumor transcriptomics is new strategy
#PancreaticCancer #PDAC #PrecisionOncology #Transcriptomics #GemPred
🧵 MTAP loss in gastrointestinal cancers: common event or actionable biomarker?
A new study in Scientific Reports evaluated >1,500 GI tumors and found MTAP loss in 25% of BTC and 30% of PDAC.
But are we ready to use MTAP in clinical practice? 👇
@Nature @NatRevClinOncol
🧵Using immunohistochemistry (IHC), MTAP loss was identified in:
🔹 25% of BTC (14/55 cases)
🔹 30% of PDAC (97/321 cases)
Nearly 1 in 3 pancreatobiliary tumors may harbor MTAP loss, supporting its potential relevance as a biomarker for emerging PRMT5-targeted therapies.
4/4 Take-home message.
Daraxonrasib showed meaningful activity across common KRAS variants including G12D, G12V and G12R.
The key lesson:
High efficacy comes at the cost of frequent dose optimisation rather than discontinuation.
Now all eyes on RASolute-302. 🔬
