SmadMinX · Stopping cancer from spreading

01The problem

Most deaths come from the spreading, not from the first tumour.

What takes lives is the spreading: cancer cells that leave the first tumour, travel through the body and grow into new tumours elsewhere, in organs such as the liver and lungs.

02What comes after

Four cancers

Oesophagus
Stomach
Pancreas
Bowel

Surgery, chemo and radiotherapy work on the first tumour. But once it has spread:

50in 100

live less than ten months.

People whose cancer had spread, across 13 cancer types: more than a million patients in the United States, 1992–2019. Those with cancer of the pancreas, the oesophagus or the stomach are among the most likely to die of it. Mani et al., Nature Communications, 2024.

03What we do

Our aim: stop the spreading after surgery.

Meant for tumours without SMAD4
Tested in mice, not yet in people

Who it can help

15 to 30 in 100 of these tumours have lost a gene called SMAD4.

Depending on the cancer. Those are the tumours the antibody is made for.

Each line is one person in 100. At least 15 lack SMAD4 Up to 30, depending on the cancer

In 40 patients' tumours we examined, 9 in 10 carried raised BMP2 or BMP4 — the two signals the antibody blocks. Eight of the 40 had lost SMAD4, and all eight carried raised levels.

04What it does

In mice, the tumours grew more slowly.

Twenty-eight days of treatment, in mice carrying a human tumour that had lost SMAD4. The antibody on its own slowed growth against saline; together with chemotherapy it slowed further.

Tumour size at day 28

Saline≈ 970

Chemotherapy≈ 670

Our antibody≈ 480

Antibody + chemotherapy≈ 360–400

In cubic millimetres. Thirty mice over six groups; the paper does not give a number per group. The four values are read off the published graph, not stated in the paper's text. In mice — not in people.

Only where the gene is gone
In human tumour cells that still had a working SMAD4, blocking the two signals changed nothing we could measure. In cells that had lost it, the cells became far less resistant to chemotherapy.
The mice kept their weight
Over the whole 28 days. Chemotherapy damaged the gut lining; adding the antibody did not make that worse.
It reached the tumour
Labelled antibody was at the tumour within half an hour, and could still be found there a day later. Three mice.

05Where it stands

Almost twenty years of work. The next step is people.

Not a bright idea from last year. One question, followed from the laboratory bench to a molecule that is now being made ready for the clinic.

Results in mice do not always carry over to people.

Almost 20 years ago
The question
Why do tumours that have lost the gene SMAD4 behave so much worse? The answer turned out to be two growth signals, BMP2 and BMP4, that nothing holds back any more.
2022
Published, and open to read
The cell and mouse results appeared in Cellular Oncology, free for anyone to read and check — including every number on this page.
2024
SmadMinX
A company, so that the work can leave the university and be made ready for patients rather than for the next paper.
Today
Tested in mice
Not yet in people. No study has started, and the drug is not available to anyone.
About 30 months
A first study in people
Longer in the body, the right patients, safety in animals. Only once those three are done can the first study be asked for.