Pharma

Agios: You may not have to kill cancer to conquer it

Killing cancer cells isn’t the only way to keep the disease at bay, researchers are […]

Killing cancer cells isn’t the only way to keep the disease at bay, researchers are learning: Coaxing immature, ill-developed cancer cells to return to their normal function is an alternate approach to controlling malignancies.

It’s described nicely in a piece by New Yorker staffer and Harvard medicine chair Jerome Groopman: The Transformation – Is it possible to control cancer without killing it? He writes:

In medical school, we were taught that although cancer comes in many forms, it has one immutable characteristic: it is composed of immature cells. The research on these blood cancers, however, suggests that this trait may be reversible after all, and that the cancer cells, when prompted to mature, become susceptible to therapies to which they would otherwise remain resistant.

The story, worth reading in its entirety, focuses pretty heavily on the early stage clinical trial work done by Cambridge biotech Agios and its drug candidate, AG-221. More specifically, it began with its impressive early success rate in Phase 1 safety trials of patients with acute myeloid leukemia, one of the more dangerous forms of blood cancer – and how its approach of identifying genetic recurrences and modifications in metabolic enzymes could be the key in developing targeted therapeutics with truly minimal side effect profiles. Why? Because the drugs won’t be killing anything – just making the cells do what they’re actually supposed to do. Agios describes its approach:

Cancer cells become addicted to certain fuel sources and inherently alter their cellular machinery to change how they consume and utilize nutrients such as the sugar glucose. Inhibiting key enzymes in cancer cell specific metabolic pathways has the potential to disrupt tumor cell proliferation and survival without affecting normal cells, thus providing a powerful new intervention point for discovery and development of novel targeted, cancer therapeutics.

And the piece continues:

The critical question is how long the benefits of AG-221 will last. “The issue is durability,” Martin Tallman, the chief of the Leukemia Service at the Memorial Sloan Kettering Cancer Center and a professor at Weill Cornell Medical College, told me. “Some patients have been in remission for six to eight months. But, based on prior studies in acute leukemia, the concern is that these people may ultimately relapse.” Tallman believes that the next step in treatment should involve combining AG-221 with a chemotherapy drug, as well as with other targeted inhibitors of gene mutations, or with bone-marrow transplantation.

Indeed, while Agios’ approach is pretty distinct, it’s not the first time scientists have used it to attack cancer. Thirty years ago, researchers found they could treat acute promyelocytic leukemia with a substance called ATRA, that matured stunted cancer cells, and then killed them off with an arsenic-based compound. Today, the disease is practically curable with this approach – but it remains fairly unique in cancer treatment.

The researchers behind ATRA were actually inspired by a passage from the Analects of Confucius: “If you use laws to direct the people, and punishments to control them, they will merely try to evade the punishments, and will have no sense of shame. But if by virtue you guide them, and by the rites you control them, there will be a sense of shame and of right.”

Researcher Zhen-Yi Wang later wrote, “If cancer cells are considered elements with ‘bad’ social behavior in our body, ‘educating’ rather than killing these elements might represent a much better solution.”

Shares0
Shares0