Science: Protein may become a new breakthrough in cancer treatment!
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Science: Protein may become a new breakthrough in cancer treatment!
Researchers at the University of California, San Francisco and San Diego have mapped out how hundreds of mutations in two cancers affect protein activity, and protein is the ultimate cause of cancer. This work points out the direction for identifying new precision therapies that may avoid many of the common side effects of chemotherapy.
Nevan Krogan, director of the Institute of Quantitative Biosciences at the University of California, San Francisco, said, “This is a new method of cancer research.” Three related papers have been published in the journal. “We realized that we needed another way to study cancer, not just using DNA.”
Krogan and Ideker turned their research objects to proteins. Proteins perform most of the functions in the human body, and their types far exceed genes, providing a broader perspective for the study of cancer.
Ideker said: “We are moving the discussion about cancer from a single gene to a protein, which allows us to understand how different mutations in patients have the same effect on protein function,” he pointed out that this work demonstrates the power of the new technology— -Explain the effects of mutations in a more precise way. “We have made the first map to observe cancer through the interaction between proteins.”
The activity of mapping these maps, known as the Cancer Cell Mapping Initiative (CCMI), is revealing the genetic patterns and organizational principles behind this disease on a huge scale, as well as potential new therapies. New research by the research team describes this therapy in detail and highlights its findings when applied to breast and head and neck cancers.
Our genes contain instructions to make proteins. It then interacts with other proteins, almost always in large groups called complexes. These protein complexes usually regulate activity or turn on/off functions. If the gene is mutated, the resulting protein complex will also mutate.
These genetic mutations can affect the work of the resulting protein complex. For example, specific interactions between two proteins may be essential for repairing damaged DNA. If the shape of the mutant version of one of the proteins is different from the normal protein, it may not interact with the other proteins correctly, and the DNA may not be repaired, leading to cancer.
Ideker said that currently, doctors treat a small number of mutated genes as biomarkers (i.e., quantifiable indicators, such as the presence of specific molecules that indicate physical conditions) to help them determine whether a certain cancer drug is beneficial to patients.
He said: “The problem is that we only found a few genes that can be used in this way to help guide the prescription of FDA-approved drugs. Our research provides a new biomarker definition, not based on a single gene or protein, but It’s based on a large multi-protein complex.”
Krogan said that there are some genes that are commonly mutated in cancer, and each of these genes can be mutated in hundreds of different ways. In addition, specific proteins may have different functions in different types of cells, so mutations in breast cancer cells may have different effects on protein complexes than the same mutations in larynx cells.
The goal of CCMI is to map protein complexes formed by about 60 genes commonly associated with breast cancer or head and neck cancer, and to observe how each gene looks in healthy cells. At the same time, he also mapped how hundreds of gene mutations in two cancer cells affect protein complexes.
Doing so brings huge computational challenges. CCMI’s collaboration allows the research team to use advanced data analysis to reveal whether mutations affect protein interactions, and the extent of their effects. Ideker said: “This detail shows us the effects of existing drugs, or explains why existing drugs can’t work.”
The authors say that the most powerful aspect of these extensive protein interaction maps is that they can provide the same insights for many other diseases. For example, they are also conducting similar studies to study protein interactions in mental and neurodegenerative diseases and infectious diseases.
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. These collaborations create an infrastructure that enables teams to integrate a range of information and promote the possibility of applying data science to complex diseases.
Krogan said: “We are fully capable of taking advantage of this change at all levels. I am now very excited that we can have such a breakthrough in cancer.”
Reference:
www.science.org/doi/10.1126/science.abf3066
www.science.org/doi/10.1126/science.abf2911
www.science.org/doi/10.1126/science.abf3067
Science: Protein may become a new breakthrough in cancer treatment!
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