Discovery may pave way for better cancer drugs

A new study has made a breakthrough discovery that could lead to the development of better cancer treatments by targeting a specific protein complex.
The study focused on mTOR, a protein at the center of two different complexes (mTORC1 and mTORC2) that play key roles in cell signaling and growth signals.
Researchers found that blocking only the mTORC2 complex, without affecting mTORC1, could shut down growth signals to cancer cells, providing a potential new approach for cancer treatment.
The discovery addresses a challenge in current cancer treatments, which often target both mTORC1 and mTORC2 complexes, leading to unintended effects such as making cancer cells more resistant to chemotherapy.
The findings have significant therapeutic implications and could lead to the design of new drugs that target the “cancer-relevant” side of the pathway without triggering survival pathways that protect tumors.

A button with the word "cancer" on it crossed out with a red line.

A new study could have important implications for the development of new classes of cancer therapeutics.

Interrupting one function of a protein that plays a key role in cell signaling could enable the development of new cancer treatments, according to the new study

Cells communicate with each other and sense their environment using protein networks called signaling pathways, says Martin Taylor, an assistant professor of pathology and laboratory medicine at the Warren Alpert Medical School of Brown University who is affiliated with Brown’s Center on the Biology of Aging and Legorreta Cancer Center.

The more important a pathway is for cell survival, the more likely it is to be hijacked by cancer cells. The most commonly altered pathway in cancer is PI3K–mTOR–Akt, and the team’s discovery centers on mTOR, the protein at its center.

What makes mTOR unusual is that it is the working engine of two different protein complexes, mTORC1 and mTORC2, and each does something different. Most cancer drugs targeted at mTOR affect both complexes—a challenge, Taylor says, because shutting down the mTORC1 complex has the unintended effect of making cancer cells more resistant to chemotherapy.

In the study published in Science, Taylor and a team of scientists showed how mTORC2 recognizes its targets, and how blocking only the mTORC2 complex, without touching mTORC1, could shut down growth signals to cancer cells.

The findings suggest a path toward new cancer treatments—something the researchers are already working on.

“This helps point the way toward designing drugs that target the cancer-relevant side of the pathway without triggering survival pathways that protect the tumor,” says Taylor, first author of the study.

“We are excited to share this story because we were able to answer a number of open questions that are important in basic biology and also have therapeutic implications.”

Source: Brown University

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Q. What is the significance of discovering how mTORC2 recognizes its targets?

A. The discovery helps point the way toward designing drugs that target the cancer-relevant side of the pathway without triggering survival pathways that protect the tumor.

Q. Why is it challenging to develop new cancer treatments targeting mTOR?

A. Most cancer drugs targeted at mTOR affect both mTORC1 and mTORC2 complexes, which can lead to unintended effects such as making cancer cells more resistant to chemotherapy.

Q. What is the most commonly altered pathway in cancer?

A. The PI3K–mTOR–Akt pathway is the most commonly altered pathway in cancer.

Q. Who is the first author of the study on mTORC2 and its role in cancer treatment?

A. Martin Taylor, an assistant professor of pathology and laboratory medicine at Brown University, is the first author of the study.

Q. What does mTOR do differently in two different protein complexes, mTORC1 and mTORC2?

A. Each complex has a distinct function: mTORC1 is involved in growth signals to cancer cells, while mTORC2 recognizes its targets but does not directly promote cell growth.

Q. How can blocking only the mTORC2 complex without affecting mTORC1 lead to shutting down growth signals to cancer cells?

A. By targeting only the mTORC2 complex, the researchers were able to block the pathway that promotes cell growth in cancer cells without triggering survival pathways that protect the tumor.

Q. What are the therapeutic implications of this discovery?

A. The findings suggest a path toward new cancer treatments by enabling the development of drugs that target the cancer-relevant side of the pathway without triggering survival pathways that protect the tumor.

Q. Who is Martin Taylor affiliated with at Brown University?

A. Martin Taylor is affiliated with Brown’s Center on the Biology of Aging and Legorreta Cancer Center.

Q. What is the significance of understanding protein networks called signaling pathways in cell communication?

A. Cells communicate with each other and sense their environment using protein networks called signaling pathways, which play a key role in cell survival and cancer development.

Q. Why is it important to understand how mTORC2 recognizes its targets?

A. Understanding how mTORC2 recognizes its targets can help researchers design more targeted and effective cancer treatments that minimize the risk of triggering survival pathways that protect the tumor.