Nav: Home

Getting a GRiP on chemoresistance: A review of GRP78 as a therapeutic target in cancer

February 28, 2018

Innate or acquired resistance to current standard-of-care therapies is a major hindrance to successful chemotherapeutic intervention. There is a critical need to elucidate the underlying mechanisms responsible for chemoresistance in order to accelerate the development of more efficacious treatment strategies.

Endoplasmic Reticulum (ER) stress response proteins are produced by cells undergoing periods of stress and facilitate the folding of proteins. The studies highlighted in this review article by researchers from the Hill Lab at the University of Notre Dame, show that ER stress response proteins are also overexpressed in cancer cells, and are often associated with high resistance to chemotherapy and poor prognosis. Specifically, elevated expression of GRP78, the master regulator of the unfolded protein response, has been shown to induce chemoresistance and serves as a indictor of poor prognosis in patients with a variety of cancers.

This review focuses on the role of GRP78 in regulating signaling pathways that control cell survival and draw attention to its value as a prognostic marker and therapeutic target. It shows that elevated GRP78 expression is predictive of resistance to chemotherapy and tumor resurgence in many cancers. Moreover, GRP78 regulates chemoresistance through several branches of the unfolded protein response as well as through modulation of the PI3K/AKT pathway.

Elevated GRP78 expression has been linked to the failure of a growing number of current standard-of-care therapies, which suggest that it is necessary to identify strategies to inhibit GRP78 function in order to sensitize chemotherapy-resistant tumors to currently available treatment regimens.
-end-
Author:

Dr. Reginald Hill and Dr. Jenifer B. Gifford,
Archibald Assistant Professor of Cancer Biology
Department of Biological Sciences
Harper Cancer Research Institute
University of Notre Dame
574-631-9962 (Office)
574-631-4420 (Lab)
http://blogs.nd.edu/hilllab/

For more information, visit: https://benthamscience.com/journals/current-drug-targets/

Bentham Science Publishers

Related Chemotherapy Articles:

Less chemotherapy may have more benefit in rectal cancer
GI Cancers Symposium: Colorado study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.
Male fertility after chemotherapy: New questions raised
Professor Delbès, who specializes in reproductive toxicology, conducted a pilot study in collaboration with oncologists and fertility specialists from the McGill University Health Centre (MUHC) on a cohort of 13 patients, all survivors of pediatric leukemia and lymphoma.
'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.
Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.
Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.
Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.
A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.
Chemotherapy or not?
Case Western Reserve University researchers and partners, including a collaborator at Cleveland Clinic, are pushing the boundaries of how 'smart' diagnostic-imaging machines identify cancers -- and uncovering clues outside the tumor to tell whether a patient will respond well to chemotherapy.
Researchers use radiomics to predict who will benefit from chemotherapy
Using data from computed tomography (CT) images, researchers may be able to predict which lung cancer patients will respond to chemotherapy, according to a new study.
How drugs can minimize the side effects of chemotherapy
Researchers at the University of Zurich have determined the three-dimensional structure of the receptor that causes nausea and vomiting as a result of cancer chemotherapy.
More Chemotherapy News and Chemotherapy Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 2: Every Day is Ignaz Semmelweis Day
It began with a tweet: "EVERY DAY IS IGNAZ SEMMELWEIS DAY." Carl Zimmer – tweet author, acclaimed science writer and friend of the show – tells the story of a mysterious, deadly illness that struck 19th century Vienna, and the ill-fated hero who uncovered its cure ... and gave us our best weapon (so far) against the current global pandemic. This episode was reported and produced with help from Bethel Habte and Latif Nasser. Support Radiolab today at Radiolab.org/donate.