In their 2019 paper, Fung et al. explore cellular signaling in malignant brain cancers, especially glioblastoma (GBM), one of the deadliest forms of brain cancer. The authors focus on “signaling convergence nodes”, which are points where multiple cellular communication pathways intersect, and the phenomenon of “pathway cross-talk,” which refers to how these pathways influence each other. Understanding these points offers potential targets for treatment. Instead of attacking one pathway at a time, targeting convergence nodes could interrupt cancer growth more effectively. The paper highlights the complexity of GBM’s signaling networks and suggests that rather than focusing on isolated pathways, treatments should aim to affect these intersections for better results.
The Fight Against Brain Cancer
Imagine if we could rewire cancer from the inside. Glioblastoma, the most aggressive type of brain tumor, resists nearly all treatments (like radiation, surgery, chemotherapy). None have led to long-term cures. One reason is that GBM isn’t just one disease. It’s a tangled web of disrupted signaling pathways that feed into each other, keeping cancer cells alive and aggressive.
Scientists are turning to something called cAMP, a small molecule with big potential. cAMP, short for cyclic adenosine monophosphate, is a “second messenger” that helps relay signals inside cells [2]. It doesn’t just switch things on or off- it can reprogram entire networks of cell behavior. But here’s the catch: GBM doesn’t play fair. Its signaling networks are like a hydra- cut off one head, and two more grow back. This makes single-target therapies frustrating. In fact, one of the key challenges highlighted by Fung et al. is how glioblastoma exploits signaling “cross-talk” to adapt and survive. It learns and evolves [3].
This is why targeting convergence points is a good idea. It’s not just about shutting off cancer’s fuel. It’s about turning the entire engine against itself [3].
Recent studies, including those discussed by Fung et al., suggest that increasing cAMP levels in GBM cells can disrupt these convergence nodes. Elevated cAMP has been shown to push tumor cells toward differentiation (where they stop multiplying) or even trigger cell death. We could use cAMP to send out a global “stop growing” signal. We can use the cell’s own communication system to calm the chaos [2].
Why It Matters
This idea isn’t just interesting for scientists. Glioblastoma patients and their families know the heartbreak of this disease. If cAMP could become part of a new treatment strategy, even as a complementary therapy, it could bring hope to a space that desperately needs it. More broadly, this research asks us to rethink how we approach complex diseases- not by fighting harder, but by listening more closely to how cells talk to each other. Could similar strategies work for other adaptive diseases, like treatment-resistant infections or autoimmune conditions?
Rethink, Rewire, Respond
Here’s the takeaway: glioblastoma’s strength is in its networks. But that might also be its weakness. By targeting how cancer cells communicate, especially through convergence points like those involving cAMP, we can fight against one of the most deadly brain cancers.
[1] Fung, N. H., Grima, C. A., Widodo, S. S., Kaye, A. H., Whitehead, C. A., Stylli, S. S., & Mantamadiotis, T. (2019). Understanding and exploiting cell signalling convergence nodes and pathway cross-talk in malignant brain cancer. Cellular Signalling, 57, 2–9. https://doi.org/10.1016/j.cellsig.2019.01.011
[2] Tisdale, M. J. (1979). The significance of cyclic AMP and cyclic GMP in cancer treatment. Cancer Treatment Reviews, 6(1), 1–15. https://doi.org/10.1016/S0305-7372(79)80056-0
[3] Wang, P., Huang, S., Wang, F., Ren, Y., Hehir, M., Wang, X., Cai, J., & Wanjin, H. (2013). Cyclic AMP-Response Element Regulated Cell Cycle Arrests in Cancer Cells. PLoS ONE, 8(6). https://doi.org/10.1371/journal.pone.0065661
