Science: Looking at cancer from the perspective of DNA

Proteins perform most of the functions in the human body, in various forms, far surpassing our genes, providing a broader perspective on the potential activity of cancer

"We will discuss cancer from a single gene protein, let's see how we see patients with different mutations affect the same protein function," Ideker said, noting that this work represents the ability of new technology to explain the impact of mutations in a more precise way

The effort to map these effects, called the Cancer Cellular Atlas Initiative (CCMI), has revealed the genetic patterns and organizational principles of this disease on a huge scale, as well as potential new ways to address it

The team’s new research details this method and highlights its findings when used in breast and head and neck cancers

From genetic mutation to protein destruction

Our genes contain instructions to make proteins

These gene mutations will affect the efficiency of the protein complex

Ideker said that currently, doctors treat a small number of mutated genes as biomarkers — quantifiable indicators, such as the presence of specific molecules that indicate physical conditions — to help them determine whether a particular cancer drug may be beneficial to patients

"The problem is that we only found a few genes, and we can use this method to help guide the prescription of FDA-approved drugs

Mapped protein mutations

Some genes in cancer are usually mutated, and each of these genes can be mutated in hundreds of different ways

The goal of CCMI is to map the constellation of protein complexes composed of approximately 60 genes commonly associated with breast cancer or head and neck cancer, and to observe how each gene looks in healthy cells

Doing so is a huge computational challenge

"This kind of detail shows us how effective existing drugs may be, or explains why it doesn't work

The authors say that the most powerful aspect of these broad protein interaction maps is that they can provide the same information in many other situations

Ideker and Krogan believe that the CCMI collaboration is the real source of power behind this approach

"We not only establish connections between different genes and proteins, but also establish connections between different people and different disciplines," Krogan said

Krogan said: "We are in a perfect position to take advantage of this revolution on all levels

Journal Reference :

1. Danielle L.
   Swaney, Dana J.
   Ramms, Zhiyong Wang, Jisoo Park, Yusuke Goto, Margaret Soucheray, Neil Bhola, Kyumin Kim, Fan Zheng, Yan Zeng, Michael McGregor, Kari A.
   Herrington, Rachel O’Keefe, Nan Jin, Nathan K.
   VanLandingham, Helene Foussard, John Von Dollen, Mehdi Bouhaddou, David Jimenez-Morales, Kirsten Obernier, Jason F.
   Kreisberg, Minkyu Kim, Daniel E.
   Johnson, Natalia Jura, Jennifer R.
   Grandis, J.
   Silvio Gutkind, Trey Ideker, Nevan J.
   Krogan.
   A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity .
   Science , 2021; 374 (6563) DOI: 10.
   1126/science.
   abf2911