Ovarian Cancer

Research
Principal Investigators: Dr. Alberto Ocaña y Dr. Atanasio Pandiella..
Centres: Albacete University Hospital Complex, CHUA and Cancer Research Centre (Centro de Investigación del Cáncer – CIC), Salamanca.

Background:

Ovarian cancer is a very frequent type of tumour in women. In fact, it represents the 6th most frequent tumour, and its incidence is increasing every year in Spain. It has a high mortality rate, as there are no early reliable detection methods and it is usually diagnosed when it has already spread..

Project Description:

The groups headed by Alberto Ocaña and Atanasio Pandiella in Salamanca collaborate in the search for new treatment alternatives for these tumours. Based on tumour samples, or on information taken from international databases, bioinformatics analyses are performed to search for patterns or specific genetic alterations that:

  • Set a possible new therapeutic target.
  • Explain resistance mechanisms to therapies used in clinical practice.
  • Characterise the tumours of patients who respond to treatments and those who don’t.
  • Define action mechanisms of new drugs under development, in order to accelerate their development and optimisation.

Once the bioinformatics analyses are performed, their results are checked and validated by means of laboratory experiments on cell lines and animals.

 

Advancements this year (2018-2019):

In their search for new therapeutic targets, these research groups have achieved excellent results.

On the one hand, they have analysed samples from a great many patients at a phosphoproteomic level. This means that they are analysing a large number of proteins that act as switches in the cell to control various mechanisms such as multiplication, survival, etc. (key processes in cancer). Phosphoproteomic analysis analyses the number of switches present and whether they are switched on or off. They have found that in a great many ovarian tumours, HER2 is augmented and activated, a key protein in certain breast cancers (read more here) that is treated with drugs such as trastuzumab or TDM1, as we can see in the illustration below:

PICTURE

The results, published in the journal Oncotarget, are very important, because they could pave the way for possible therapies in cases of more complicated ovarian cancer. Other proteins have also been identified, and the teams are currently working on analysing their importance as possible targets for attack.

DNA is like a vast library that contains all the information a cell needs to live. This information can be extracted in small volumes, called transcripts, which indicate which cellular functions are operating. Depending on the transcripts, a cell can behave differently; it can divide, move, grow, and even commit suicide… Analysis of the transcripts for ovarian cancer cells has revealed two new potential therapeutic targets, EZH2 and UBE2, in a study published by the group in Cancer Medicine. They are also currently working intensely on finding ways of attacking these targets.

The Immunotherapy Project for Ovarian Cancer has also been launched. Several molecules have been detected that could be characteristic of ovarian tumour cells. Right now the team is working on ascertaining the relevance of these molecules, before designing antibodies against them. They are also analysing molecules that might help the immune system to detect tumour cells and eliminate them by not considering them normal cells.

Furthermore, they have recently begun evaluating the therapeutic potential of a new class of compounds. These compounds, called degraders, have the potential to bond to certain key proteins in the development of tumours, and mark them out. This mark would mean that the cell machinery itself would identify that protein as something to be destroyed. If tumour cells depend on certain proteins and we could eliminate them, this would help the body to fight against tumour cells.

Achievements pre 2018:

The group has published two significant scientific papers regarding Bet-type protein inhibitors, which have been shown to be very effective against ovarian tumour cells. They have also shown the effectiveness of a new combination of compounds, called Aurora A and CHEK1 inhibitors. These results are important, as around 10% of women suffering from ovarian cancer have the Aurora A and CHEK1 mutations.