CNIO Friends Newsletter 43

Dear Friends,

Over the past few months, we have made some important discoveries, one of which even made the front cover of the prestigious Nature journal, as you will see in this newsletter. We are very proud of our achievements and hope they will speed up progress in the diagnosis and treatment of cancer, as well as other diseases. I would also like to share with you some of the other initiatives we have launched during this period.

First of all, I would like to thank you for all the affection and generous support we received this year for the CNIO Friends Day. On 30th June, we all got together to celebrate this annual meeting of our community of donors, all of you who have made it possible to launch our CNIO Friends International Contracts Programme to attract research talent to our Centre. At long last we were able to hold this event in person once again, after it was put on hold because of the COVID-19 pandemic, in a moving and emotional open day at CNIO headquarters. Over the course of the day, almost a hundred CNIO Friends learned more about some of the cancer research projects we are able to run thanks to your solidarity. It was such a great pleasure to present our work to you in person. For those of you who were unable to come, this newsletter provides more information and also a video of the day, which I encourage you to watch and share with as many people as possible.

I would also like to highlight in particular the launch, once again thanks to your tremendous support, of a new edition for the CNIO Friends International Contracts Programme. We are now offering nine new contracts for cancer researchers. These scientists will have the opportunity to carry out cutting-edge cancer research projects. The aim of this programme is to keep talented young researchers in Spain and to open up new lines of cancer research on metastases, breast cancer, kidney and liver tumours, among others. Thanks to the CNIO Friends International Contracts Programme, so far a total of 26 researchers have been able to develop their research over the course of a two-year placement at CNIO.

Finally, I would like to celebrate with you the launch of a new edition of CNIO Arte. This will be the sixth edition of this project launched with the support of Fundación Banco Santander, which explores the synergies between art and science. CNIO Arte 2023 will take place in February 2023, coinciding with the ARCO art fair –at which, as you will remember, we have had our own stand for the last two years− curated by the sculptor Marina Vargas.

All that’s left for me to do now is to wish you a great summer. I am looking forward to meeting again in the autumn, to continue sharing promising initiatives and moving forward together in the fight against cancer.

Maria A. Blasco
Director

Laura works in the Microenvironment and Metastasis Group (CNIO) lead by Héctor Peinado. The main objective of her research is to find new targets to block melanoma metastasis and prevent the development of resistance to applied therapies. Specifically, Laura investigates the use of the NGFR small molecule inhibitor (THX-B) as anti-metastatic therapy in melanoma, alone or in combination with current immunotherapies, as well as the underlying mechanisms in these processes.

Laura has always wanted to focus on cancer in her work, because she knows how much it affects society and wanted to be able to contribute in a meaningful way. In her PhD she focused on the oncogenic signalling pathways governing primary tumor development but she has now moved to the study of metastasis and the interplay between tumor cells and their microenvironment at distal places, knowing that these two features determine the poor prognosis and the outcomes of melanoma patients.

After finishing her PhD, Laura moved to New York to work as a post-doc in Dr. Lyden’s lab (Weill Cornell Medicine), with the idea to learn state-of-the-art technologies in the tumor microenvironment from a world leading laboratory. However, it was always in her mind to try and secure a position at the CNIO. She says “Having the option to work in such a globally recognised centre in my home of Madrid was an incredible opportunity, and I am so grateful to the CNIO Friends Fellowship.”

Laura has particularly enjoyed the way that the CNIO works – she finds it to be very well organised, and especially appreciates the work of the core units at the Centre.  She explained that the core units (for example, flow cytometry, confocal microscopy, histopathology and the animal facilty) help researchers implement projects by providing invaluable technical support. As she explained “As a researcher, you design the experiment in your head and then the staff in the core units can help you implement it and make sure everything is done well.” She also enjoys the great amount of seminars and opportunities to discuss scientific initiatives during the CNIO lab day, the progress reports or the distinguished seminars.

Regarding her CNIO Friends funded project, Laura told us “We are studying melanoma because it is a very metastatic disease. We need to try to stop the metastatic process because it is the main cause of death in most cancers. In my project, I am trying to combine immunotherapies with a drug treatment that blocks metastasis development. We need to find a way to implement current therapeutic options and also be able to block the resistance to immunotherapies, which is another big problem in cancer treatment nowadays.”

In terms of her motivation for her work going forward, Laura explained “Ideally, I would like to get to the place in society where cancer is a chronic disease that can be managed, with low rates of mortality. To do that we need to find durable responses to provide a way for people to live a long and relatively healthy life, even with cancer.”

At the recent CNIO Friends Day held at the Centre, Laura was really inspired to have the opportunity to meet people who generously commit their own funds into cancer research. She was particularly inspired to hear how much our donor community really believe in what the CNIO researchers are doing. Laura found this really encouraging and wants to say thank you to you all, once again, for supporting our cancer research.

Nature. Developing a biomarker that will enable the most serious cancers to be effectively treated. Researchers at CNIO and the Cancer Research UK Cambridge Institute have developed a method to decipher the genetic chaos of the deadliest cancers and use this information to treat them more effectively. Their work is described in an article published in Nature, one of the most prestigious scientific journals in the world. The research has been co-directed by Geoff Macintyre, head of the CNIO Computational Oncology Group, and Florian Markowetz, senior researcher at the Cancer Research UK Cambridge Institute (UK), working alongside CNIO researcher Bárbara Hernando and scientists from other British, Canadian, Belgian, and German institutes.

More information

Journal of Advanced Research. CNIO researchers identify cryptic vulnerabilities in a key oncoprotein for the development of new anticancer drugs. The Kinases, Protein Phosphorylation and Cancer Group at the CNIO, led by Iván Plaza Menacho, has been able to identify structural and dynamic details in the action mechanism of these inhibitors, which were previously unknown. “We have known about the crystalline structure of the catalytic RET domain coupled to these compounds since last year, but  these cryptic pockets within the active centre have not been identified until now since they are not always available because they are subject to dynamic and conformational changes that are not always captured with the crystalline structure,” explains Iván Plaza.

More information

EMBO Molecular Medicine. Discovering a ‘weak spot’ that makes multi-drug resistant tumours vulnerable again. CNIO researchers have discovered one of the causes of the multi-drug resistance displayed by some tumours, and a potential strategy for overcoming it. This new ‘weak spot’ can be exploited using existing drugs, which kill tumour cells by activating their stress responses. In addition, the paper, published today in EMBO Molecular Medicine, “helps us understand why several oncology therapies already in use work,” says lead author Óscar Fernández-Capetillo.

More information

Summer arrived and brought with it our most moving and emotional event of the year, the Annual CNIO Friends Day, aimed at all of you, our dear CNIO friends, a community that grows with each passing year. A day on which we opened up our doors and our arms to you to thank you all in person and, among other activities, show you the impact of your donations and the latest achievements and advances of the centre.

In case you missed it, you can watch all the presentations here, including the one given by the director of the centre Maria Blasco, and listen to the different questions asked by some of the friends who attended.

Eva Nogales, a leading international figure in the field of molecular biophysics and structural biology, who is carrying a sabbatical at CNIO as part of the Fundación Jesús Serra Visiting Researchers programme, gave a master seminar at the centre.

Summer is a busy time here at CNIO: we welcome university students who will be spending their summer with us, learning what life is like at one of the most important cancer research centres in Europe.

Over the summer, the centre has also launched other important initiatives. These include the CNIO-PharmaMar project to test possible drugs against micro-metastases of breast cancer. CNIO has also signed a license with American biotech firm Totus Medicines to develop a new generation of molecules against cancer. Running parallel to this, the CNIO Biobank has received €800,000 from the EU, which will certainly help us to continue making progress.

Australian researcher Geoff Macintyre has just developed a biomarker that will make it possible to treat the most serious cancers more effectively. His research has been featured on the cover of the June issue of the journal Nature.

What have you and the team discovered?

Cancers such as pancreatic, esophageal, lung and ovarian are difficult to treat resulting in poor survival rates. This is because the DNA in these tumours is completely chaotic. The genomic chaos prevents the use of state-of-the-art precision medicine tests to choose the right therapy for a patient. However, we have developed a method to make sense of the genomic chaos that uses computational approaches to find patterns in the DNA which represent the some of the fundamental causes in these cancers.

Why is that important?

We can use the fundamental cause identified in a tumour to select which drug a patient will respond to. In our study we showed that specific DNA patterns found in a tumour can predict response to commonly used platinum-based cheomotherapy in ovarian and esophageal patients. This is important for the patients that are resistant to the drug, as they may be able to avoid the toxic side-effects and have a chance at receiving another drug that might work. We also showed that other patterns could predict response to 44 new drugs under development. This has the potential to fast-track clinical trials for these therapies. Finally, we also showed that the patterns can be used to identify new drug targets, which may result in better therapies that will benefit more patients in future.

When will we see your results translated to the clinic?

The development of new therapies using this approach is still 10-years away but the use of this technology to better treat patients for existing therapies may only be a few years away. To maximise this benefit, we have spun-out a company Tailor Bio, which is designed to rapidly translate this technology to the clinic.

Researcher Eva Nogales has been officially announced as the latest beneficiary of the Fundación Jesus Serra Visiting Researchers programme. Nogales, a biophysicist born in Madrid, has worked for years at the Lawrence Berkeley National Laboratory in California (USA). She is a member of the Department of Molecular and Cellular Biology at the University of California in Berkeley and a researcher at the Howard Hughes Medical Institute.

The Fundación Jesús Serra programme funds research stays in Spain for researchers who have developed their career at international centres over the last five years. Once a year, CNIO welcomes leading experts in their field, who come to the Centre for several months.

Nogales graduated with a degree in Physical Sciences from the Universidad Autónoma de Madrid in 1988. She earned her PhD from Keele University (UK) in 1992, while working on the synchrotron radiation source under the supervision of Joan Bordas.

Her research focuses on proteins that are genuine molecular machines, responsible for some of the central functions of living beings. One of the molecular machines that have fascinated Nogales throughout her career is tubulin. This protein is used to build microtubules, cylinders that fill and shape the cell and play a key role in cell division.

In 1998, Nogales made the cover of Nature journal with her discovery of the three-dimensional structure of tubulin, a challenge pursued by numerous researchers for decades. She achieved this after five years of working within her specialist field of electron cryomicroscopy. At present, she is still studying microtubule dynamics.

Throughout her career, Nogales has resolved structures that were thought to be virtually unresolvable. In addition to tubulin and microtubules, she has unravelled the structure of human telomerase and the human polycomb repressive 2 complex (PRC2). In recognition of her pioneering work, Nogales was elected a member of the National Academy of Sciences in the US  and the American Academy of Arts and Sciences, as well as a foreign member of the European Molecular Biology Organization.