Cancer should be viewed not just as rogue cells, but as a complex system with its own supply chains and communication infrastructure. This perspective shift justifies novel therapies like Zelenorstat, which aim to dismantle this entire operating system by cutting its power source.
Experiments show that transferring a cancer cell's dysfunctional mitochondria—but not its nucleus—into a healthy cell is what induces cancer. This disruptive finding supports the view of cancer as a metabolic disease that can be targeted by starving its mitochondria of fuels like glucose.
Dr. Levin reframes cancer as a cognitive problem where the bioelectric "glue" binding cells into a collective fails. Cells lose their large-scale purpose and revert to an ancient, single-cell state. Restoring this electrical communication can normalize tumors without killing the cells, presenting a non-destructive therapeutic approach.
Step Pharma's synthetic lethality approach targets two redundant enzymes in the same pathway. Deleting one makes cancer cells entirely dependent on the other. This direct dependency is harder for biology to circumvent compared to approaches targeting different, interconnected pathways, creating a "cleaner" kill mechanism.
An innovative strategy for solid tumors involves using bispecific T-cell engagers to target the tumor stroma—the protective fibrotic tissue surrounding the tumor. This novel approach aims to first eliminate this physical barrier, making the cancer cells themselves more vulnerable to subsequent immune attack.
Zelenorstat inhibits NMT, an enzyme that attaches a "GPS tag" to proteins, guiding them within the cell. By blocking this process, it renders key cancer-driving proteins useless, effectively confusing the cancer's operating system rather than using brute-force poison like chemotherapy.
Despite billions invested over 20 years in targeted and genome-based therapies, the real-world benefit to cancer patients has been minimal, helping only a small fraction of the population. This highlights a profound gap and the urgent need for new paradigms like functional precision oncology.
Traditional targeted cancer therapies inhibit or 'cool down' overactive pathways, like pumping brakes on a runaway car. Delpha Therapeutics employs a counterintuitive 'activation lethality' approach, further over-activating pathways to 'overheat the engine' and cause catastrophic failure in cancer cells—a fundamentally opposite but highly effective strategy.
The same cellular mechanism (NMT) hijacked by cancer cells is also exploited by viruses like HIV and coronaviruses for replication. By inhibiting NMT, Zelenorstat could potentially halt viral spread, making it a candidate for future pandemic defense.
Instead of just killing cancer cells, the primary mechanism is to insert a gene that forces the infected cell to produce and secrete a potent drug, like an anti-PD-L1 antibody. This creates a hyper-concentrated therapeutic effect directly in the tumor microenvironment, a concept termed "molecular surgery."
Instead of searching for elusive natural markers to target, EARLI's platform creates its own. It programs synthetic genetic "switches" that activate only inside cancer cells, turning them into factories that produce their own cancer-fighting therapies. This shifts the paradigm from biological discovery to biological engineering.