Cancer — 2

When reviewing a slide of a tumor biopsy, we used to just say a person’s cancer tissue was heterogeneous—that is, not uniform. But now spatial biology goes much deeper in its analysis to reveal the evolutionary background landscape of the tissue—a sort of cellular time machine. Cells can be barcoded to track their fate, sequencing their mitochondrial DNA, the relative abundance of tumor clones over time in different parts of the body, and differentiate nonmalignant processes, such as clonal proliferation of blood stem cells (hematopoiesis). It had long been recognized that approximately 25 percent of cancers are preceded by chronic inflammation at the site of the tumor origin, but we recently learned that a type of intestinal T cell is capable of initiating cancer on its own. Notably, spatial mapping of the pancreas in healthy adults demonstrated hundreds of small cancer precursor lesions called PanINs (short for pancreatic intraepithelial neoplasia), almost all of which contain KRAS (the leading driver gene of pancreatic cancer) hot spot mutations. Given how many PanINs people have, it’s amazing more cancers don’t develop in us. Our bodies have strong defenses.

Alongside high-tech mapping, treating patients has enlightened us. A woman who developed breast cancer at the age of fifty-one had precursor clones of cancer evident at thirteen. Another woman diagnosed at fifty-three had cancerous clones at seventeen. A gap of more than ten years was found from the appearance of driver mutations to founder cancer cells, another substantial lag to diagnosis. This is a long road to cancer, on which we can detect its occurrence at a precancerous state, and certainly before it has spread from its site of origin to other parts of the body.

This is a profoundly powerful insight. It’s a key to unlocking tools we can use against all the major age-related diseases, providing opportunities to change their natural history. We can prevent these diseases years before they become full blown.