Understanding cancer is like assembling IKEA furniture.
Hear me out. Both start with individual pieces that make up the final product. For a cabinet, it’s a list of labeled precut plywood. For cancer, it’s a ledger of genes that—through the Human Genome Project and subsequent studies—we know are somehow involved in cells mutating, spreading, and eventually killing their host.
Yet without instructions, pieces of wood can’t be assembled into a cabinet. And without knowing how cancer-related genes piece together, we can’t decipher how they synergize to create one of our fiercest medical foes.
It’s like we have the first page of an IKEA manual, said Dr. Trey Ideker at UC San Diego. But “how these genes and gene products, the proteins, are tied together is the rest of the manual—except there’s about a million pages worth of it. You need to understand those pages if you’re really going to understand disease.”
Ideker’s comment, made in 2017, was strikingly prescient. The underlying idea is seemingly simple, yet a wild shift from previous attempts at cancer research: rather than individual genes, let’s turn the spotlight on how they fit together into networks to drive cancer.
Together with Dr. Nevan Krogan at UC San Francisco, a team launched the Cancer Cell Map Initiative (CCMI), a moonshot that peeks into the molecular “phone lines” within cancer cells that guide their growth and spread. Snip them off, the theory goes, and it’s possible to nip tumors in the bud.
This week, three studies in Science led by Ideker and Krogan showcased the power of that radical change in perspective. At its heart is protein-protein interactions: that is, how the cell’s molecular “phone lines” rewire and fit together as they turn to the cancerous dark side.
One study mapped the landscape of protein networks to see how individual genes and their protein products coalesce to drive breast cancer. Another traced the intricate web of genetic connections that promote head and neck cancer.
Tying everything together, the third study generated an atlas of protein networks involved in various types of cancer. By looking at connections, the map revealed new mutations that likely give cancer a boost, while also pointing out potential weaknesses ripe for target-and-destroy.
For now, the studies aren’t yet a comprehensive IKEA-like manual of how cancer components fit together. But they’re the first victories in a sweeping framework for rethinking cancer.
“For many cancers, there is an extensive catalog of genetic mutations, but a consolidated map that organizes these mutations into pathways that drive tumor growth is missing,” said Drs. Ran Cheng and Peter Jackson at Stanford University, who weren’t involved in the studies. Knowing how those work “will simplify our search for effective cancer therapies.”
Cellular Chatterbox
Every cell is an intricate city, with energy, communications systems, and waste disposal needs. Their secret sauce for everything humming along nicely? Proteins.
Proteins are indispensable workhorses with many tasks and even more identities. Some are builders, tirelessly laying down “railway” tracks to connect different parts of a cell; others are carriers, hauling cargo down those protein rails. Enzymes allow cells to generate energy and perform hundreds of other life-sustaining biochemical reactions.
But perhaps the most enigmatic proteins are the messengers. These are often small in size, allowing them to zip around the cell and between different compartments. If a cell is a neighborhood, these proteins are mailmen, shuttling messages back and forth.
Rather than dropping off mail, however, they deliver messages by physically tagging onto other protein. These “handshakes” are dubbed protein-protein interactions (PPIs), and are critical to a cell’s function. PPIs are basically the cell’s supply chain, communications cable, and energy economy rolled into one massive infrastructure. Destroying just one PPI can lead a thriving cell to die.
PPIs ar...