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Wide-ranging research

Whilst many research groups are studying

Myc, there have been major barriers to

inhibiting the onco-protein, in addition to the

potentially harmful effects on patients.

Soucek explained more: “Myc is located

inside the nucleus of a cell, and that is usually

considered an area where we are unable to

send any inhibitor. Furthermore, many drugs

currently used in the clinic are small

molecules that target active or catalytic sites

in enzymes or kinases. Instead, Myc is a

transcription factor, and does not have such a

site that can be inhibited.

“Another reason is that Myc is not just one

protein, it’s a family of proteins and these

proteins can replace each other in some

situations. Consequently, whatever inhibitor we

choose to use, it needs to be able to inhibit

them all, adding another complication.

“Finally, Myc is also required for some critical

physiological processes, and consequently the

dogma has been that inhibiting Myc would cause

catastrophic side effects in normal cells and

tissues; hence Myc has long been considered an

untouchable, ‘undruggable’ protein.”

Breakthrough

The ERC-funded researcher then detailed her

successful creation of a Myc inhibitor and some

subsequent experiments undertaken.

“During my time as a student, almost 20 years

ago, I designed a Myc inhibitor. This Myc

inhibitor is called Omomyc, and we first used it

in cancer cells in culture and saw that it was

very efficient at inhibiting Myc.

“As a result, we undertook an assessment to

see whether the inhibitor would be safe. After

moving from Italy to the United States, I

undertook research on cancer mouse models.

It was there we were able to test the inhibitor

B

acked by the European Research Council, a major

investigation is underway in Spain that has the potential to

develop a treatment for many human cancers. The project

‘Pushing Myc inhibition towards the clinic’, or MYCINHIBINCLINIC,

is funded by a five-year €1.7m Consolidator Grant awarded in 2013

to Dr Laura Soucek at the Vall d’Hebron Institute of Oncology (VHIO)

in Barcelona, Spain.

To find out more about the project, Portal spoke to Soucek, who outlined

the background to studying the onco-protein Myc, the creation of an

inhibitor, and the wide-ranging benefits that could be brought to

patients. The researcher began by outlining the core emphasis of the

ERC-funded investigation.

“The focus of this project is Myc, an onco-protein that is upregulated or

deregulated in the majority of human cancers. Myc is a master regulator

of several cellular functions, that is to say, it controls all the programmes

that instruct the cell to grow and divide.

“Normally, Myc’s regulation is very finely tuned – the Myc protein gets

turned on only when it’s needed, and then gets turned off when its task

is over. For example, Myc is only expressed when a tissue needs to

regenerate or grow, or in the case of healing a wound.

“However, in cancer, the Myc protein is deregulated and is never turned

off. Therefore, it keeps instructing the cells to divide, leading to

tumourigenesis. The aim of this ERC project is to find an efficient and

safe way to inhibit Myc.”

I S S U E S E V E N

H O R I Z O N 2 0 2 0 P R O J E C T S : P O R TA L

www.horizon2020projects.com

146

C A N C E R & C A R D I O V A S C U L A R D I S E A S E

Unexpected discovery

Following an unexpected breakthrough concerning a Myc inhibitor,

Portal

spoke to ERC-funded scientist

Dr Laura Soucek

about the dramatic potential

in tackling cancer and the subsequent development of a drug

Dr Laura Soucek

©KathrinWermke

Structure of the c-Myc

(red) in complex with

Max (blue) and DNA