Nav: Home

Study finds novel molecular therapeutic target for colon cancer

January 13, 2020

(Boston)--Researchers have found a way to help make chemotherapy more effective in treating colon cancer. They identified a new pathway (RICTOR/mTORC2) as a biological target for the disease. Targeted inhibition of RICTOR or the mTORC2 pathway could be used as a distinctive therapeutic opportunity with chemotherapy for treating colon cancer.

"Identification of biological targets to enhance sensitivity to chemotherapy is becoming a priority for effectively treating cancers to reduce toxicities caused by chemotherapy or to overcome resistance," explained corresponding author Sam Thiagalingam, PhD, associate professor of biomedical genetics, medicine and pathology & laboratory medicine and pharmacology & experimental therapeutics at Boston University School of Medicine (BUSM).

Previous studies by Thiagalingam and his colleagues found that SMAD4 gene mutations correlate to an advanced stage of colon cancer and SMAD4 acts as a metastasis suppressor by interacting to block the functionality of transcription factors that promote metastatic cancer progression. Furthermore, clinical data and studies performed using cell culture systems by Thiagalingam and others found that loss of or low SMAD4 expression is associated with poor response to 5-fluorouracil, the backbone of almost all chemotherapy combinations used in the treatment of metastatic colon cancer.

The researchers hypothesized that SMAD4 could elicit the metastatic suppressor function not only by blocking functionality of transcription factors but also by disabling metastasis promoting signaling pathways. "We found for the first time that SMAD4 interacts with RICTOR to suppress mTORC2 functionality and therefore the loss of SMAD4 function results in oncogenic activation of the mTORC2 pathway, leading to enhancement in metastatic colon cancer progression and resistance to chemotherapeutic agents," said Thiagalingam.

According to the researchers, this study suggests that effectiveness of cancer therapies involving chemotherapeutic agents such as irinotecan for colon, pancreatic or other cancers eliciting defect in SMAD4 functionality would be highly effective when combined with targeted inhibition of RICTOR/mTORC2 pathway.

In addition to colon cancer, poor prognosis has been associated with mutations, deletions and low levels of SMAD4 in gliomas and pancreatic, prostate and lung cancers.
-end-
These findings appear online in the journal Molecular Cancer Research, a journal of the American Association for Cancer Research.

Funding for this study was provided by a grant from NIH/NCI (CA165707), an integrated pilot grant funded by the Boston University Clinical & Translational Science Institute (NIH/NCATS award 1UL1TR001430), Carter Pilot Award for Diversity and Cancer Equity from Boston University Cancer Center and a seed grant from the Boston University Genome Science Institute to S.T. C.K.W is a recipient of the Boston University Cross Disciplinary Training in Nanotechnology for Cancer (XTNC), BUnano, and Susan G. Komen Mentoring and Training in Cancer Health Disparities (MATCH) fellowships.

Boston University School of Medicine

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

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
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

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.