If normal cells are law-abiding citizens, then cancers are outlaws, says scientist Vasan Yegnasubramanian, M.D., Ph.D., the Director of inHealth Precision Medicine at Johns Hopkins. “They’re like rogue citizens who break the rules, corrupt or coerce other citizens to behave in ways that can support the cancer and cause the city to enter into chaos. When we observe that chaos, it appears that every cancer is very different, and seems way too complex to understand and figure out ways to treat it. This is what happens in prostate cancer.”

But Yegnasubramanian and a team of researchers had an idea: what if, despite all the differences among prostate cancers, they share a similar origin story – a molecular reason why they went rogue? A recent study with scientists from across the Johns Hopkins School of Medicine has shown that activation of a powerful gene called MYC is a chaos-producing event that most prostate cancers have in common.

“To understand how MYC activation could lead to the complex spectrum of alterations we see in prostate cancer and surrounding cells, we couldn’t just observe human tissues,” Yegnasubramanian explains. “We needed to watch the process unfold over time, by studying mouse models that mimic human prostate cancer.”

In a groundbreaking study using cutting-edge single-cell sequencing and molecular pathology technologies, they showed that activation of MYC in the cancer cells generated signals “that started to give them capabilities such as higher metabolism to fuel their growth.” Then, “to our surprise, we saw that this initial activation of MYC also set off an alarm system in the cells,” a flurry of activity: “Genes were expressed that signaled to immune cells, the body’s police force, that something was wrong. But strikingly, the MYC-activated cancer cells eventually figured out ways to shut off these alarm bells! They even figured out how to corrupt some of the immune cells and other nearby cells to help them evade the policing immune cells. Switching off those alarm bells and evading the immune surveillance paved the way for the MYC-activated cells to become invasive, and to completely disrupt the surrounding cells.”

These findings, published in the journal Nature Communications, represent a major advance in understanding the complex nature of prostate cancer and its environment.

“They suggest that the activated MYC gene could be orchestrating a series of changes that transform the normally harmonious cellular city into a dystopia taken over by invading cancer cells.” Now, armed with this new understanding, scientists can look for ways to deactivate or shut down MYC, and perhaps prevent or even reverse the damage caused by prostate cancer.