A step closer to cancer precision medicine

Researchers from the Faculty of Medicine and the Institute for Molecular Medicine (FIMM) at the University of Helsinki have developed a computational model, Combined Essentiality Scoring (CES) that enables accurate identification of essential genes in cancer cells for development of anti-cancer drugs.

Why are the essential genes important in cancer?

Cancer is the leading cause of death worldwide. Cancer cells grow faster usually with the activation of certain genes. Targeted therapies aim at inhibiting these genes that are activated only in cancer cells, and thus minimizing side effects to normal cells.

High-throughput genetic screening has been established for evaluating the importance of individual genes for the survival of cancer cells. Such an approach allows researchers to determine the so-called gene essentiality scores for nearly all genes across a large variety of cancer cell lines.

However, challenges with replicability of the estimated gene essentiality have hindered its use for drug target discovery.

"shRNA and CRISPR-Cas9 are the two common techniques used to perform high-throughput genetic screening. Despite improved quality control, the gene essentiality scores from these two techniques differ from each other on the same cancer cell lines," explains Wenyu Wang, first author of the study.

How can we do better?

To harmonize genetic screening data, researchers proposed a novel computational method called Combined Essentiality Scoring (CES) that predicts cancer essential genes using the information from shRNA and CRISPR-Cas9 screens plus molecular features of cancer cells. The team demonstrated that CES could detect essential genes with higher accuracy than the existing computational methods. Furthermore, the team showed that two predicted essential genes were indeed correlated with poor prognosis separately for breast cancer and leukaemia patients, suggesting their potential as drug targets (Figure 1).

"Improving gene essentiality scoring is just a beginning. Our next aim is to predict drug-target interactions by integrating drug sensitivity and gene essentiality profiles. Given the ever-increasing volumes of functional screening datasets, we hope to extend our knowledge of drug target profiles that will eventually benefit drug discovery in personalized medicine," says Assistant Professor Jing Tang, corresponding author of the study.

Wenyu Wang, Alina Malyutina, Alberto Pessia, Jani Saarela, Caroline A Heckman, Jing Tang.
Combined gene essentiality scoring improves the prediction of cancer dependency maps.
EBioMedicine, November 12, 2019. doi: 10.1016/j.ebiom.2019.10.051.

Most Popular Now

Findings open way for personalised MS treatment

Currently available therapies to treat multiple sclerosis (MS) lack precision and can lead to serious side effects. Researchers at Karolinska Institutet in Sweden have no...

Pfizer shares top-line results from Phase 2/3 EPIC…

Pfizer Inc. (NYSE: PFE) shared top-line results from the Phase 2/3 EPIC-PEP (Evaluation of Protease Inhibition for COVID-19 in Post-Exposure Prophylaxis) study evaluating...

Pfizer and Biohaven's VYDURA® (rimegepant) granted…

Pfizer Inc. (NYSE: PFE) and Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN) today announced that the European Commission (EC) has granted marketing authorizatio...

A smarter way to develop new drugs

Pharmaceutical companies are using artificial intelligence to streamline the process of discovering new medicines. Machine-learning models can propose new molecules that ...

Cognitive impairment from severe COVID-19 equivale…

Cognitive impairment as a result of severe COVID-19 is similar to that sustained between 50 and 70 years of age and is the equivalent to losing 10 IQ points, say a team o...

Foundation S: Sanofi's new philanthropic spearhead

Sanofi today launches Foundation S - The Sanofi Collective, its philanthropic endowment fund aiming to create healthier futures for generations. Using donations, partners...

SK bioscience and GSK's adjuvanted COVID-19 vaccin…

SK bioscience and GSK announced submission of a biologics license application for SKYCovione™ a recombinant protein-based COVID-19 vaccine candidate adjuvanted with GSK’s...

Investigational COVID mucosal vaccine protects aga…

In animal studies that mimic human exposures, an investigational COVID vaccine designed to be taken orally not only protects the host, but also decreases the airborne spr...

Using AI to analyze large amounts of biological da…

Researchers at the University of Missouri are applying a form of artificial intelligence (AI) - previously used to analyze how National Basketball Association (NBA) playe...

Asthma drug can block crucial SARS-CoV-2 protein

A drug used to treat asthma and allergies can bind to and block a crucial protein produced by the virus SARS-CoV-2, and reduce viral replication in human immune cells, ac...

Recurring brain tumor growth is halted with new dr…

When a non-metastatic brain tumor - a meningioma - recurs after surgery and radiation treatment, a patient is out of options. No drugs are approved for these aggressive t...

Pfizer to acquire Biohaven Pharmaceuticals

Pfizer Inc. (NYSE: PFE) and Biohaven Pharmaceutical Holding Company Ltd. (NYSE: BHVN) have entered into a definitive agreement under which Pfizer will acquire Biohaven, t...