2. Cancer stem cells: origins, resistance, metastasis (and diet)

Cancer cells are far from homogenous, both in terms of genetics and epigenetics. There seems to be a hierarchical structure established inside a tumor, a sort of tree whose roots store what are known as stem cells. Although it is still somewhat controversial, quite a few studies grant them fundamental properties: based on epigenetic mechanisms, they're the only ones able to start a tumor (if other tumor cells are transplanted into mice, the tumor doesn't grow), they divide very slowly and, above all, they're particularly resistant to chemotherapy. This is why cancer can reappear if even one of these cells remains, even though treatment originally seemed to work.

For John Edgar Dick, a professor at the University of Toronto and a pioneer in research in this field, “If cancer stem cells are so significant, and tumors grow and evolve from them, then their characteristics are the most important." But studying them is a challenge, as is developing treatments to beat them. "Stem cells have many properties that allow them to escape from therapies," explained Dick. "If they're at the core of tumor evolution, it's difficult to beat Darwin."

“If cancer stem cells are so significant, and tumors grow and evolve from them, then their characteristics are the most important”

Metastases

In the end, most cancer deaths are due to metastasis, the journey cancer cells take through the body. For this to happen, some of them must take on very specific properties: through fundamentally epigenetic mechanisms, they become more "liquid", detaching easily from the tumor mass. But they also have to be able to start a new tumor wherever they nest, so they have to have the characteristics of stem cells.

The group led by Salvador Aznar − ICREA researcher at the Institute for Research in Biomedicine Barcelona (IRB) and scientific leader of this B·Debate along with Eduard Batlle and Raúl Méndez− has tried to identify the cells in a tumor that trigger metastasis, and in the process has come across some remarkable surprises: the cells responsible “look like adipocytes,"^[3] explained Aznar and, in fact, they have many upregulated genes associated with fat metabolism. Specifically, a receptor called CD36, which imports fatty acids to the cell, is abnormally active in the cells.

The data is both hopeful and alarming: CD36 seems to be necessary to trigger metastasis, and blocking it with antibodies dramatically decreases the process in mice. However, the finding, published in Nature, also leads to questions, like the ones Aznar himself wonders, "So, is there a link between diet and metastasis? Could that explain the increase in mortality seen recently in some types of cancer?" That could be the case. "We consume a lot more fatty acids than we think, even in normal, everyday products," said Aznar. It's too soon to extract conclusions but, from the wide range of those possible, one seems particularly worrying: palmitic acid, found in vegetable oils like coconut and palm oil.

Another surprising, cutting-edge study is that led by Eduard Batlle, ICREA researcher and head of the Oncology Program at IRB Barcelona. Metastasis is the most clinically relevant process in colon tumors and his group has observed that “the genes that predict a poor prognosis are expressed not in the tumor but in its surroundings,” Batlle explained. It seems that cancer changes its surroundings to make it easier for it to spread and that “gives us a chance to treat it” by focusing on the area around the tumor.

One way could be to attack the TGF beta molecule, which seems to be an important regulator of the process. However, this approach is complex; in the initial stages it may, paradoxically, play a protective role. Batlle’s team has attempted to identify which tumors could benefit from this treatment. In the laboratory, the results are promising, and surprisingly better when combined with new forms of immunotherapy. 

[3] Adipocytes are the cells that make up adipose or fat tissue.