1. From biology to new treatments
Although it is not an exclusively female tumor (far from it), the history of lung cancer is in good part a history of how our approach to cancer has evolved in recent years. This history was summed up in the inaugural speech by Silvia Novello, professor of medical oncology at the University of Turin, and is about small, increasingly specific and unique, steps in the fight against the enemy with a thousand faces.
“In 2005, therapies weren’t very effective and barely had an average survival rate of one year,” explained Novello. But then came new approaches. In 2008, doctors started using new drugs that target the blood vessels and subtypes of tumors began being treated differently. And, in 2010, the concept of precision medicine was truly introduced, with drugs targeting specific mutations (like those in the EGFR gene). Since then, new drugs, targets and markets have appeared and, at the same time, we have seen that, although the steps forward have been substantial, it isn’t enough. Tumors generally end up becoming resistant, so studies and new drugs are launched to overcome the resistance. In addition, in the midst of this escalation, immunotherapy has appeared, opening a new door (still in the early days) for hope.
Lung cancer is increasingly common among women; as they started smoking later, the cases have started increasing at an alarming rate in recent years. Breast cancer, on the other hand, is overwhelmingly a female cancer (although not exclusively), and there are several parallels to the approach to lung cancer, with subtypes treated in different ways.
In some cases, the treatments are quite successful thanks in large part to precision medicine. In others, however, the options don’t have the desired results. This is the case of what are known as “triple negative” tumors, a definition that alludes to the lack of targets for treatment that others do have.
“When people ask me if we’re making headway with this type of tumor, my answer is yes. But we still have a long road ahead,” said Carey Anders, professor of Medicine at the University of North Carolina. Through extensive genetic analysis, scientists are working to find specific gene signatures to guide treatment. For example, by inhibiting androgen receptors or proteins that repair DNA. And, in the end, “whether we like it or not, all oncologists are turning into immunologists,” confessed Anders, alluding to the new forms of immunotherapy. “The results aren’t great yet, but we’re starting to see that, the sooner we start treatment the more effective it is.”
Biological knowledge is allowing researchers to conduct trials with breast cancer therapies that weren’t originally designed for this disease. “Some patients could benefit from a drug that is currently being prescribed for osteoporosis,” explained Eva González Suárez, researcher at IDIBELL Barcelona and co-leader of this B·Debate. They are RANK pathway inhibitors, which curb bone degeneration and seem to also play a role in developing mammary tissue. Clinical trials are already scheduled to discover their true value.
Other studies are working to untangle the role obesity plays in cancer, specifically in breast cancer. “We know that not only does the risk increase but also the prognosis is worse. Specifically, the risk of metastasis is higher,” said Daniela Quail, professor at the Goodman Cancer Research Centre in Montreal, Canada. Her studies have found it is tied to greater inflammation, more immunosuppressive white blood cells and molecular messengers like those known as GM-CSF or interleukin IL-5. This opens the door to not only personalizing dietary interventions, but also trying to cut off some of those messengers using specific antibodies.
María Blasco, director of the Spanish National Cancer Research Center (CNIO) in Madrid, presented her latest results in the fight against multiform glioblastoma, a particularly serious brain tumor. It is not found only in women, but her work is world renowned and “she is a benchmark as a woman in research,” explained Eva González Suárez. For years, her group has studied the role of telomeres in cancer, as the structures that act as an “expiration date” for cells and that many tumors manage to regenerate in order to effectively become immortal. They previously tried with drugs that had failed, “surely because they selected cells with the longest telomeres, as with cancer stem cells.” This meant that part of the tumor could hang on and grow back.
Now they have tried a different approach, “attacking the action of telomeres, more than their length.” The results have been spectacular in lab mice and they are already designing drugs to be used in clinical trials. At the same time, they are also studying “the biology of stem cells and the role of resistances, which will surely appear,” says Blasco.
Another, less known, part of research focuses on the tumor environment, where it develops. The group led by Frances Balkwill, professor of Cancer Biology at the University of London, has found a signature of 22 genes expressed in this environment that predicts a better or worse prognosis for ovarian cancer, “a tumor whose survival rate hasn’t changed much in recent years,” recognized the researchers. Plus, the genes in the signature “could also be shared by other types of cancer.”
On the role of the environment and the structure in which cells grow, particularly emphatic and provocative were the words of Mina Bissell, an extremely prestigious researcher at the Lawrence Berkeley National Laboratory, in the United States. “We accumulate mutations, but the cancer doesn’t appear until the architecture is damaged,” she explained. Bissell says, “We know almost everything about the genome, but we know nothing about the language of shapes,” which is why so many studies sequencing DNA haven’t come up with hardly any treatments. “Text books are important, but they can be corrupted because they seem to want to be written in stone,” she warned. And she concluded with a final suggestion: “Don’t get arrogant. The most famous scientists are arrogant. Why? It kills the passion.”