Current Research in Relation to Arne’s Current Condition

Feb 14, 2026

To our wonderful community: thank you so much for the influx of messages and articles regarding the latest breakthroughs in pancreatic cancer. Many of you have reached out about Daraxonrasib (also known as RMC-6236) and the recent headlines regarding the triple-drug cocktail of Daraxonrasib, Afatnib, and SD36 that successfully eradicated the cancer cells in mice along with many other smaller scale studies.

We are so incredibly grateful that you act as our "eyes and ears," keeping a lookout for every potential ray of hope. It means the world to us that you are thinking of Arne and scanning the horizon for any possible lead. While these scientific milestones are exciting and we look forward to the day they become available for patients, unfortunately, these have not been applicable to Arne.

Many of these findings, while groundbreaking, are not yet ready for human trials or have very specific requirements that don't currently align with Arne's situation. Additionally, as his medical profile has become more complex—particularly with the recent vascular changes and his specific genetic markers—he is precluded from many of these specific trials and medications at this time.

The medical team does their best, but they don't always have all the answers. That is why we are so blessed to have you all looking out for us. We continue to keep our own eyes and ears open, holding onto every bit of hope for Arne.

For those who have asked for more detail, below are the current facts regarding Arne’s condition and his molecular profile:

--------------------------------------------------------------------------------
1. Executive Clinical Summary

Current Diagnosis: Stage IV (Metastatic) Pancreatic Ductal Adenocarcinoma.
Primary Tumor: Head/uncinate process of the pancreas (approx. 5.5 x 5.7 cm).
Spread: Metastases to the liver (multiple bilobar lesions) and peritoneum (carcinomatosis).

Current Status: Progressive disease on first-line chemotherapy (mFOLFIRINOX). Currently on second-line therapy (Gemcitabine/Abraxane) and anticoagulation for new acute portal vein thrombosis.

--------------------------------------------------------------------------------
2. Genetic and Molecular Profile: Outlook Analysis

Arne’s tumor has undergone extensive profiling (Caris, Tempus, and Ambry Genetics). Below is the breakdown of each mutation and its impact on his prognosis and treatment options.

A. Somatic (Tumor) Mutations

1. KRAS p.G12D (Driver Mutation)
• Status: Detected (Variant Allele Fraction ~25%).
• Outlook: Negative.

• Explanation: This is the primary "driver" of his cancer. It is a Gain of Function (GOF) mutation that locks the cell growth switch in the "on" position. KRAS mutations are associated with aggressive disease and resistance to therapies. While drugs exist for G12C mutations, there are currently no FDA-approved targeted therapies specifically for G12D in pancreatic cancer, limiting him to standard chemotherapy or clinical trials.

2. TP53 p.R175H
• Status: Detected.
• Outlook: Negative.

• Explanation: TP53 is a tumor suppressor gene (the "guardian of the genome"). This mutation causes a Loss of Function, meaning cells cannot repair DNA damage or trigger cell death when they should. This is associated with chromosomal instability and resistance to chemotherapy.

3. SMAD4 (Copy Number Loss)
• Status: Detected.
• Outlook: Negative.

• Explanation: Loss of SMAD4 is a hallmark of advanced pancreatic cancer. It is statistically associated with a higher likelihood of distant metastasis (specifically to the liver) rather than just local growth. This correlates with Arne's rapid development of multiple liver metastases.

4. CDKN2A and CDKN2B (Copy Number Loss)
• Status: Detected.
• Outlook: Negative.

• Explanation: These genes regulate the cell cycle. Their loss removes the "brakes" on cell division, contributing to uncontrolled tumor growth.

5. HER2 (ERBB2) Amplification
• Status: Positive. (IHC was 2+/Equivocal, but FISH confirmed amplification with a copy number of 7.65).
• Outlook: Potentially Positive.

• Explanation: While rare in pancreatic cancer, HER2 amplification is a clinically actionable target. Although not standard of care, this opens the door for targeted therapies (like Trastuzumab deruxtecan) in a clinical trial setting or as an off-label option if standard chemotherapy fails.

6. Microsatellite Status (MSS) & Tumor Mutational Burden (TMB)
• Status: Microsatellite Stable (MSS); TMB-Low (3.2 mut/Mb).
• Outlook: Negative.

• Explanation: This profile indicates the tumor is "cold" to the immune system. Tumors that are MSS and TMB-Low generally do not respond to immunotherapy (checkpoint inhibitors like Keytruda).

B. Germline (Hereditary) & Pharmacogenomics

1. Hereditary Cancer Panel (77 Genes)
• Status: Negative (No pathogenic mutations in BRCA1/2, Lynch genes, etc.).
• Outlook: Neutral/Positive.

• Explanation: The cancer is sporadic (random), not inherited. This is positive for his children as they are not at elevated genetic risk. However, it is negative for treatment because BRCA mutations would have opened up options for PARP inhibitors (e.g., Olaparib).

2. DPYD Activity
• Status: Normal Metabolizer (Activity Score 2.0).
• Outlook: Positive.

• Explanation: He can safely metabolize 5-FU based chemotherapy without high risk of severe toxicity. (Though he has now moved past this therapy).

**3. UGT1A1 Genotype (1/
• Status: Intermediate Metabolizer (Heterozygous).
• Outlook: Mixed.

• Explanation: This genotype makes it harder to metabolize Irinotecan, increasing the risk of severe diarrhea and neutropenia. This likely explains why he experienced diarrhea during his initial FOLFIRINOX treatment. This information is less relevant now that he has switched to Gemcitabine.

--------------------------------------------------------------------------------
3. Clinical Progression Summary

Anatomic Progression (The "Negative" Trends)

• Vascular Occlusion (Critical): As of Feb 8, 2026, the tumor has caused new complete occlusion of the portal vein and portal confluence due to tumor thrombus. This causes venous congestion in the bowel and accelerates fluid buildup.

• Ascites: He has developed moderate volume malignant ascites/fluid retention, requiring a 4-liter drainage on Feb 13. This masks his true body weight and indicates peritoneal spread.

• Liver Metastases: Despite the Histotripsy procedure in December destroying part of the primary tumor, the metastatic disease in the liver has worsened, with lesions growing in size and number.

Palliative & Functional Status (The "Positive" Interventions)

• Biliary Stent: The transition to a metallic stent in Jan 2026 was successful. His bilirubin is normal (1.0 mg/dL), and the external drain was removed, significantly improving his daily quality of life.

• Pain Control: Following SBRT (radiation) to the pancreas on Feb 4, 2026, he reported his pain control is still the same as before.

• Chemo Tolerance: He seems to be tolerating the new regimen (Gemcitabine/Abraxane) better than the previous FOLFIRINOX.

Conclusion
Arne’s disease is driven by aggressive KRAS G12D and SMAD4 mutations which drive metastasis and resistance. The outlook is currently guarded due to the vascular occlusion and liver progression. However, the identification of HER2 amplification provides a unique, non-standard therapeutic target for the future, and his current palliative interventions (stent, radiation) have successfully stabilized his immediate quality of life.

{{name}}

{{formatted_created_at}}