Cancer treatments are always progressing: in addition to diagnostic and surgical improvements, in recent years there has also been a whole battery of new drugs based on precision medicine, drugs that target the specific particularities of each tumor in each patient.

Nevertheless, a new obstacle has arisen in the fight. Tumors are able to evolve and adapt to the treatment, becoming resistant. In a way they behave like an infection trying to survive. To overcome this resistance, researchers are working on different approaches: analyzing the full genetics of tumors to better understand them and define better treatments, monitor their evolution and detect their weaknesses; at the same time, they are researching drug combinations to make it more difficult for tumors to escape their action; and for the past few years, they have been developing what is called oncology immunotherapy, the great hope in the fight against cancer in recent years, based on stimulating the body’s own defenses to attack and control tumors. And all with sights set on the rising price of drugs, which threatens to make it difficult for the general public to afford them.

In order to present and discuss the latest advances, challenges and difficulties in the fight against cancer, national and international experts met for a B·Debate, an initiative of Biocat and the “la Caixa” Foundation to promote scientific debate.

• Cancer treatments have improved prognosis in recent years, however the resistance tumors develop to treatments has been underestimated and is now the greatest obstacle facing the fight against cancer.
• Immunotherapy, which consists in stimulating our own defenses to fight tumors, is the great hope in oncology, and this is where much research is being focused.
• Large-scale genetic studies are allowing us to better understand the characteristics of each tumor and its weaknesses. The therapies of the future will be drug combinations to make it more difficult for tumors to escape their action.
• The increasing price of drugs is a growing problem. Some of the solutions involve better dialog between the industry and administrations, for example through what is known as results-based agreements (the hospital only pays the industry if the drug works). 

1. Resistance to cancer treatments: a public health problem

 “20 years ago, approximately half of all people diagnosed with cancer were still alive five years later. Now it’s nearly 70%,” explained Joaquín Arribas, director of the Preclinical Research Program at Vall d’Hebron Research Institute and one of the scientific leaders of this B·Debate. About 20 years ago, we also started using cancer drugs based on precision medicine: instead of destroying all the cells that divide, like classical chemotherapy, they target specific, highly altered cells in a tumor. This tends to make them more effective and with fewer side effects. Since then, most cancer drugs have been based on this philosophy, “Of the 45 drugs approved between 2009 and 2014, nearly all are based on pharmacological targets,” said Arribas.

Nevertheless, except in very few cases, the vast majority of these drugs end up failing. Tumors act like living communities that evolve extremely quickly, like an infection. Some of them are indifferent to treatment from the very beginning. Others evolve to find a way out: they accumulate various changes in their cells aimed at helping them survive, and in many cases they do. This is why early diagnosis is important, so that surgery (alone or in combination with radiotherapy and pharmacotherapy) can get rid of all of the cells before they have a chance to evolve.

Miquel Àngel Pujana, researcher at the Catalan Institute of Oncology (ICO, IDIBELL) and co-scientific leader of this B·Debate, explained the problem in figures, “In 2015, the ICO diagnosed 1,700 women with breast cancer and 300 cases of resistance to treatment, which has a huge impact in terms of health but also on an economic level: 50% of pharmaceutical spending for breast cancer goes to treating resistances”. With this motivation, ICO and IDIBELL decided to create the ProCURE program (Program Against Cancer Therapeutic Resistance), which encompasses nine research groups all fighting this problem and is led by Pujana.

Faced with this problem, the question arises: Did we overestimate the ability of precision medicine? Arribas doesn’t think so. For example, treatments of this kind have made certain types of leukemia a chronic condition, and for some breast tumors, “We now have four lines of treatment that be used, when a few years ago we couldn’t do anything,” he said. What happened is that “we underestimated the problem because we didn’t understand it.”

Now this issue is fundamental, and there are many approaches being studied to better understand and minimize it. One of these is understanding tumor genetics and evolution so we can stimulate the immune system to fight cancer.

> Read more: 2) Tumor evolution and genetic signatures 

The rise of genetic sequencing techniques and IT tools is gradually contributing large amounts of information on tumors. Cancer isn't one single disease, there are at least 200 different types and really there are as many tumors as there are patients.