Prostate Cancer Project

Research
Principal Researcher: Dr. David Olmos y Dra. Elena Castro.
Centres: Centro Nacional de Investigaciones Oncológicas – National Oncological Research Centre (CNIO), IBIMA (Instituto de biomedicina de Málaga – Málaga Biomedicine Institute ).

Background:

Prostate cancer is the most frequent male cancer in the Western world, and its incidence increases year by year; it is already the 3rd cause of male death by cancer, after lung and colorectal cancer, with 5,400 annual deaths in Spain.

Although in a high number of cases it is curable with surgery and radiotherapy, some patients with more aggressive forms of this cancer are not diagnosed correctly and are treated with less potent therapies than they should. It is necessary, on the one hand, to improve diagnosis tools and criteria in order to be able to choose the most suitable treatments for each patient, and, on the other, to find new forms of treatment to cure the more aggressive tumours.

Project Description:

The Prostate Cancer Clinical Investigation Unit headed by David Olmos is working to develop new treatments for prostate cancer, especially in its more aggressive forms. The group is implementing a large amount of clinical trials, several of them multi-centre trials (comprising several hospitals within Spanish territory) and other smaller trials. Most of these multi-centre trials are included within the framework of the platform PROCURE.

As well as studies and projects comprised within or directly resulting from this platform, they are implementing a series of clinical and preclinical investigation projects.

Advances made this past year (2018-19)

The results of the PROREPAIR B trial are continuing to reveal important information about mutations in the genes involved in DNA repair. In this context, major advances are continuing to be made in the monitoring and treatment of patients in whom one of these genes, known as BRCA2, has mutated. This gene is proving to be essential in the understanding and treatment of prostate cancer that is resistant to conventional therapies. The PROREPAIR B study is analysing samples from a great number of patients (419) before, during, and after receiving their treatments. They then look for mutations in the proteins that repair DNA and seek to correlate these with how patients respond to different treatments.

 

PICTURE

 

The prostate cancer lab has already previously demonstrated that prostate cancer patients with inherited mutations in the BRCA2 gene (one of these repair genes) have more aggressive tumours and a worse prognosis. Furthermore, at the congress of the American Society for Clinical Oncology (ASCO) in 2018, data were presented that indicated that in patients with a mutated BRCA2 gene, the sequence of initial treatment could be important, for example, initiating treatment of the advanced disease with abiraterone or enzalutamide (which are two types of hormone treatments) and then continuing with taxanes (a type of chemotherapy) seems to be more effective than the inverse combination. This study shows the importance of genetic studies in patients when deciding on their treatment, and is hugely important in clinical practice.

Along this same line of research, the group has demonstrated that relatives of prostate cancer patients with BRCA2 mutations could be more susceptible to develop cancer, especially prostate, breast or ovarian. For this reason, they should access family cancer prevention programmes. This finding has been published in the Journal of Clinical Oncology (link). 

The importance of the work carried out by the CRIS Prostate Cancer Unit has been confirmed by the numerous awards and prizes it won in 2018. One of the most important prizes was the DoD Impact Award presented by the US Department of Defense to develop a collaborative prostate cancer project. This type of programme is rarely accessed by researchers outside of the US.

Previous Achievements:

The different trials included within the PROCURE platform (PROREPAIR, PROSTAC, PROSABI, PROSENZA, …) Have been actively recruiting in the past few months, and most patients have been tracked at least 20 months. Furthermore a study (Theratlas) will be implemented to collect samples of all these trials, in order to study the evolution of prostate tumours in the different development phases.

The group is also writing an article regarding hormonal treatments and their combination with certain corticoids, which could have a direct application in the treatment of, particularly difficult cases.

Likewise, certain laboratory studies have been commissioned to qualify patient tumours with high levels of proteins associated with poor prognoses, such as BRCA1 and 2, or mutations and proteins that help to repair DNA, such as ATM. Furthermore, they are studying, in animal models, how these proteins collaborate between them in the development of prostate tumours.

Project PROSENZA to research prostate cancer tumours is implemented with the support of the Social Work area of “la Caixa”.

Personalised Therapies in Patients with Metastatic Prostate Cancer

On the other hand, the results of the PROREPAIR B clinical trial have shown that mutations in the DNA repair gene called BRCA2 inpatients are so significant that the group plans to publish them in a high-impact publication in the next few months (they are going to sound out Lancet). In fact, the results of this clinical trial were presented orally in the ESMO (European Society for Medical Oncology) Congress, one of the foremost cancer congresses worldwide, where only the most relevant work is presented orally.

Furthermore, the group’s work has been awarded several prizes and fellowships, amongst them: Award for the best poster at the Spanish Medical Oncology Society (SEOM)(Rebeca Lozano), the Androgen Project Award (Rebeca Lozano), Travel Award by ESMO (Nuria Romero), and, especially, the Prostate Cancer Foundation Award for Dr Elena Castro.