Should I Stay or Should I Go Now?

Mar 20, 2024

In case, like us, you happened to wake up one morning and randomly wonder who or what the timeless rant, “Should I Stay, or Should I Go?”, by the English rock band, The Clash, was about, here is the explanation, courtesy of Google, from the former lead guitarist, Mick Jones, “It wasn’t about anybody specific, and it wasn’t pre-empting my leaving The Clash. It was just a good rockin’ song...”

In other words, feel free to come up with your own cancer-specific interpretation like we did. The song’s chorus, which from sometimes admittedly faulty memory, is:

Should I stay, or should I go now?
Should I stay, or should I go now?
If I stay, there will be trouble
And if I go, it will be double

This perfectly sums up the dichotomy between local and systemic disease with cancer.

Most cancers start out as local disease, which, depending on anatomical location and size, may or may not initially cause trouble. Double the trouble arrives when cancer cells ‘decide’ to metastasize, turning what was a local, and potentially curable disease into a systemic, non-curable one.

To treat metastases with surgery, chemotherapy, and/or radiation therapy is, by and large, to fight a losing battle.

By contrast, immunotherapies, such as checkpoint inhibitors (CIs), which activate the immune system against cancer cells, have shown promise to significantly prolong survival and possibly even to cure metastatic patients.

The problem with CIs is that they only benefit 20-40% of patients with specific immunogenic or “hot” tumor types like melanoma, non-small cell lung cancer, breast cancer, bladder cancer, kidney cancer, and Hodgkin’s lymphoma. In contrast, for patients with non-immunogenic or “cold” tumors such as prostate, pancreas, uterine, breast, and brain cancers, checkpoint inhibitors are typically ineffective.

Enter the oncolytic adenovirus called AdAPT-001 that is armed with a TGF-β trap. This “trap” neutralizes the protein TGF-β, which is protective for tumors, because TGF-β causes the immune system to stand down. In a Phase 2 trial, the addition of AdAPT-001 to checkpoint inhibitors made several tumors that were previously CI-resistant CI-responsive.

If AdAPT-001 proves to be the answer for CI-resistant cancer, then we propose the following chorus to sing along to:

Should I, as an oncologist, stay, or should I go now?
If I stay with an immune checkpoint, there may or may not be trouble (for tumors)

But if I also go with AdAPT-001, it will be double (for tumors)