AUG 31, 2020 9:38 AM PDT

Targeting Your Inner Hedgehog to Fight Chemoresistance in Colorectal Cancer

WRITTEN BY: Jasper Cantrell

Chemoresistance is a serious problem for many cancer therapies. Solutions to this problem are harder to come by than the medicines themselves, but a team from Sapienza University in Rome may have an answer for colorectal cancer.

Colorectal cancer is known for developing chemoresistance. However, a recent study pointed to a signaling pathway, the Hedgehog-GLI pathway, as a critical player in developing that resistance. This pathway is typically involved in regulating cell differentiation in early development but has also been linked to tumor development when dysregulated. The team decided to conduct a new study to determine how the Hedgehog- GLI pathway is involved in colorectal cancer’s chemoresistance.

The study began by examining the protein GLI, the genetic regulator involved in the Hedgehog-GLI pathway, in colorectal cancer cells after treatment with the first-line chemotherapies. The drugs both activated and upregulated GLI, and increased cancer cell death - albeit alongside a small increase to growth at low doses. Using a GLI inhibitor alongside the chemotherapy drugs suppressed this growth effect and increased the chemotherapies’ anti-cancer activity. So they knew that inhibiting GLI prevented GLI dependent growth, but how did it do it?

The team knew that a particular family of transporters, ATP-binding cassettes (ABC) transporters, were often involved in drug resistance and may play a role in Hedgehog-GLI mediated chemoresistance. They identified several down-regulated members during GLI inhibition and found that GLI overexpression coincided with the ABC transporters’ overexpression as well. This effectively linked the Hedgehog-GLI pathway to ABC transporters, which are known to facilitate chemoresistance in cancers.

This study’s data supports the idea that Hedgehog-GLI mediated chemoresistance is given by GLIs activation of certain ABC-transporters. This pathway has already been the target of several therapy studies, but the team notes that so far, many have ended poorly. However, this new information will assist with future studies by providing a viable target, GLI.

The team concludes, “Indeed, our results indicate that the addition of GLI targeting drugs to CRC treatment strategies is a therapeutic option that could prevent the onset of chemoresistance.”

Sources: Nature Scientific Reports, Science in HD, Research Square

About the Author
  • Hey everyone! My name is Jasper and, considering I am pretty new here to Labroots, I figured I would introduce myself. I received my bachelor’s from the University of California at Riverside back in 2016. I started off my career a few years ago with a job at a University over in New York, before moving over into the industry. I'm happy to be writing content for Labroots, and I hope you enjoy it!
You May Also Like
MAY 24, 2021
Health & Medicine
How do healthcare insurance disruptions affect access and affordability to care?
MAY 24, 2021
How do healthcare insurance disruptions affect access and affordability to care?
Have you ever been in between health insurance coverage and pushed off receiving healthcare that you needed? According t ...
JUN 09, 2021
Technology
Computer Program Generates Effective, Clinically-valid Treatment Plans for Cancer Patients
JUN 09, 2021
Computer Program Generates Effective, Clinically-valid Treatment Plans for Cancer Patients
In a recent study published in Nature Medicine, researchers at the Princess Margaret Cancer Centre offer evidence for th ...
JUN 11, 2021
Cancer
Man beats brain cancer with ketogenic diet
JUN 11, 2021
Man beats brain cancer with ketogenic diet
Glioblastoma brain cancer continues to be one of the most fatal cancers, responsible for approximately 15,000 death ever ...
AUG 23, 2021
Cancer
A Safe and Effective Combination Therapy for Advanced Cancer
AUG 23, 2021
A Safe and Effective Combination Therapy for Advanced Cancer
Immunotherapies are emerging as a promising strategy for the treatment of late-stage cancers which currently have m ...
AUG 25, 2021
Cell & Molecular Biology
Sino Biological's Listing on the Shenzhen Stock Exchange
AUG 25, 2021
Sino Biological's Listing on the Shenzhen Stock Exchange
China, August 16, 2021 - Sino Biological, Inc. (“Sino Biological” or the “Company”), a biot ...
SEP 06, 2021
Cancer
A New Biomarker to Personalize Breast Cancer Therapy
SEP 06, 2021
A New Biomarker to Personalize Breast Cancer Therapy
The American Cancer Society estimates that over 280,000 women in the United States will be diagnosed with breast cancer ...
Loading Comments...