The biology is on my side: KRAS wild-type, left-sided, and why round two added a targeted therapy

The following is a cut/paste from Gemini on why my specific tumor biology is favorable, and why round two looked different from round one and why today’s round three will also add that additional targeted therapy. I explained it once but it’s complicated so I wanted more information.

From GEMINI AI:

### 1. KRAS wild-type: the on-switch in my cancer still works normally

In colorectal cancer, the EGFR protein sits on the outside of a cancer cell like an antenna. When it gets activated, it fires a growth signal down a chain of proteins called the RAS pathway (KRAS, NRAS, BRAF, then RAF, MEK, ERK). That signal tells the cell to grow and divide.

In about 40 percent of colorectal cancers, the KRAS gene is mutated and that switch gets stuck in the "on" position. No matter what you do to the antenna, the growth signal keeps firing. Anti-EGFR drugs do not work in that scenario.

My tumor is **KRAS wild-type**, meaning the gene is normal. The switch only fires when the antenna tells it to. That makes my cancer vulnerable to drugs that block EGFR. This single biomarker is what unlocks an entire class of targeted therapy for me.

### 2. Left-sided primary tumor: a fundamentally different biology

The colon is not one uniform organ. The right side develops from the embryologic midgut, the left side from the hindgut. Tumors that arise in each location are biologically different.

Right-sided tumors more often carry BRAF mutations, MSI-high status, and a hypermutated profile. They tend to respond less well to standard chemo.

Left-sided tumors (mine) are more often RAS wild-type, more chromosomally stable, and far more sensitive to anti-EGFR therapy.

### 3. The combination: why round two (and beyond) added a targeted therapy

Put the two together. KRAS wild-type gives the key. Left-sided gives me the door that key unlocks. Together they make me a near-ideal candidate for adding an anti-EGFR monoclonal antibody (most likely **panitumumab** or **cetuximab**) on top of my chemo backbone.

What this combination buys, based on published data (NOTE - I DON’T know if the following applies to me)

- **Objective response rates often above 70 percent.** Most patients see real shrinkage.
- **Deep, fast responses.** Not just slowing the tumor, actively shrinking it.
- **Conversion to resectability.** This is the one I care about most. The goal of intensifying treatment now is to shrink the liver mets enough that a surgeon can take them out.

The mechanism is elegant. The antibody binds to the EGFR antenna on my cancer cells, physically blocking growth factors from docking. That shuts down the RAS/RAF/MEK/ERK and PI3K/AKT pathways. As a bonus, it flags those cells for my own immune system to attack (a process called antibody-dependent cellular cytotoxicity, or ADCC).

Side effects to expect, and what they mean:

- **Acneiform rash on the face, chest, and back.** Counterintuitively, this is a good sign. The severity of the rash correlates with how well the drug is working.
- **Low magnesium.** My kidneys will waste it, so labs and supplements will be on the schedule.
- **Paronychia.** Soreness around the nails.

### 4. What this means for the rest of my treatment

The strategy is intentional intensification. Hit hard, hit early, get the deepest response possible.

- **Restaging CT in about 2 to 3 months** to measure how much the liver mets have shrunk.
- **CEA tumor marker trending downward** is the blood-based signal we want.
- **Possible ctDNA (liquid biopsy)** to catch any resistance mutations early.
- **Surgical conversation** if the liver disease shrinks enough to consider resection.
- **Maintenance therapy** down the line, likely a lighter chemo backbone plus the targeted agent, once we have banked a strong response.

Again - the above was from AI, simply educational, not my words and not from my office visit notes. Always need to validate but it does break down the concept well.

Round Three is NOW - let’s freaking go! Thank you for walking this with me.

Love you all. ❤️🙏🥊