APPENDICURE

Appendix cancer that spreads throughout the abdomen has very few effective treatment options, especially in advanced stages. Researchers are continuing to study more precise ways to target these tumors.

A recent study by researchers at Memorial Sloan Kettering evaluated a targeted radiation approach using a platform called GPA33-SADA. The goal was to deliver radiation directly to cancer cells while limiting exposure to healthy tissue. You can read the original study here: Cures of Peritoneal Appendiceal Cancer Xenografts Using GPA33-SADA Pretargeted Alpha and Beta Radiopharmaceutical Therapy

The researchers used patient derived tumor models that closely reflect how appendix cancer behaves in the body. They tested two types of radiation:

Alpha radiation, which is highly potent and travels a very short distance
Beta radiation, which travels farther but is less intense

Both treatments were directed at a protein called GPA33, which was found on many of the tumor samples studied.

How the treatment works

This approach uses a two step process.

First, an antibody attaches to the cancer cells by targeting GPA33. This antibody is part of the SADA platform, which is designed to assemble at the tumor site and then break apart and clear from the rest of the body.

Next, a radioactive component is introduced. It binds to the antibody already attached to the tumor and delivers radiation directly to the cancer cells.

This method is designed to increase the amount of radiation that reaches the tumor while reducing exposure to normal tissues.

What types of appendix cancer this may apply to

This study focuses on appendiceal epithelial cancers that have spread throughout the abdomen. The approach may be relevant across several subtypes, depending on whether the tumor expresses the GPA33 protein.

Low grade mucinous tumors	These tumors often spread within the abdomen and produce mucin. This includes many cases of pseudomyxoma peritonei. If GPA33 is present, this type could potentially be targeted by this approach.
High grade appendiceal adenocarcinoma	These tumors tend to grow and spread more aggressively. Because they are epithelial in origin, they may express GPA33 and could be candidates for this type of targeted therapy.
Signet ring cell tumors	This subtype is less common and typically more aggressive. Expression of GPA33 can vary, but if present, the same targeting strategy could apply.
Goblet cell adenocarcinoma	These tumors have features of both glandular and neuroendocrine cancers. GPA33 expression may be less consistent, but some cases could still be targetable depending on tumor biology

Pseudomyxoma peritonei

PMP is not a separate cancer type, but a condition caused by mucin producing appendix tumors spreading in the abdomen. If the underlying tumor expresses GPA33, this approach could be relevant here as well.

What the researchers studied

The study evaluated tumor samples from patients to confirm that GPA33 and other markers were present. While several targets were identified, GPA33 was selected for treatment because it is already well studied in colorectal cancer.

The therapy was then tested in mice implanted with patient derived appendix cancer tumors. Some tumors were placed under the skin, while others were placed inside the abdomen to better reflect how the disease spreads in people.

The researchers measured:

Tumor response and survival
Distribution of the treatment in the body
Short term and long term side effects

Results from the study

In models where tumors were growing inside the abdomen:

Eight out of ten mice treated with alpha radiation had no detectable cancer at the end of the study period
Survival was significantly longer compared to untreated models
Beta radiation also improved survival, although complete responses were less frequent

In models where tumors were placed under the skin:

Both alpha and beta therapies extended survival compared to controls

The study also measured how much radiation reached the tumor compared to normal tissues. The results showed higher targeting of tumors, especially with the alpha therapy.

Side effects

The treatment was generally well tolerated in these models.

Observed side effects included:

Temporary decreases in white blood cells
Mild and reversible weight loss

No severe short term or long term toxicities were reported. Tissue analysis showed only minimal changes in the kidneys.

What we know from early human research

The same SADA platform used in this study has already been tested in a Phase 1 clinical trial in humans using colon cancer as a target.

That trial evaluated safety and dosing and reported that the platform was well tolerated. Patients received the treatment without major safety concerns. You can read about this study here: Anti-GPA33 Pretargeted Radioimmunotherapy (PRIT) of Colorectal Cancer (CRC) Using a Self-Assembling and Dis-Assembling (SADA)

This does not mean the approach has been tested yet in appendix cancer. However, it shows that the delivery system itself can be used in people, which is an important step before disease specific trials begin.

What this means

This study showed that targeted radiation using the GPA33-SADA platform was able to eliminate tumors in advanced appendix cancer models and extend survival with limited toxicity.

These results are based on preclinical models and have not yet been tested in patients with appendix cancer. Further studies are needed to evaluate safety and effectiveness in humans.

What comes next

Future steps may include early phase clinical trials to determine whether this approach can be used in patients with appendix cancer or other cancers that spread in the abdomen.

Researchers will also need to identify which patients are most likely to benefit based on tumor characteristics such as GPA33 expression.

Final thoughts

This study adds to ongoing efforts to develop more targeted treatments for appendix cancer. It demonstrates that delivering radiation directly to tumor cells may improve outcomes while reducing harm to healthy tissue.