Nav: Home

New treatment strategy may benefit patients with brain cancer

June 30, 2020

Gliomas with mutations in what are called the isocitrate dehydrogenase (IDH) genes are the most common brain tumors diagnosed in younger adults aged 18 to 45 years. Patients can benefit from aggressive surgery, along with radiation and chemotherapy treatments, but these therapies are not curative in many cases.

Now a team led by investigators at Massachusetts General Hospital has uncovered a potentially promising strategy to target these tumors and improve treatment. The findings are published in Cancer Discovery, a journal of the American Association for Cancer Research.

Prior work by the group, led by Mass General's Daniel Cahill, MD, PhD, Hiroaki Wakimoto, MD, PhD, and Julie Miller, MD, PhD, revealed that IDH mutant gliomas have a metabolic weakness making them especially susceptible to treatments that lower levels of NAD+, a ubiquitous and vital metabolic molecule commonly thought of as the "currency of metabolism" in cells.

Also, previous work by other researchers found that chemotherapy activates an enzyme that stimulates NAD+ molecules to join together to make poly(ADP-ribose), or PAR, a key DNA damage signal. This PAR signal is a known susceptibility in IDH mutant gliomas.

Researchers also discovered that activation of the enzyme by chemotherapy causes available NAD+ to be critically depleted for the production of PAR in IDH mutant glioma cells, but not normal cells.

These findings indicated that maintaining high PAR levels (and low NAD+ levels), in combination with chemotherapy, may uniquely target IDH mutant glioma cells. Considering this, Hiroaki Nagashima, MD, PhD, research fellow and lead author, devised a new treatment strategy and tested it in tumor cells and animal models.

"We found that maximum effectiveness was achieved by combining two agents: temozolomide, the chemotherapy most commonly used to treat patients with IDH mutant gliomas, with a drug that blocks PAR breakdown, known as a PAR glycohydrolase inhibitor," said Dr. Cahill, a Neurosurgical Oncologist at Mass General and an Associate Professor of Neurosurgery at Harvard Medical School.

"We showed, for the first time, that PAR glycohydrolase inhibitors can be used to enhance the effectiveness of chemotherapy in tumors with metabolic weaknesses in the NAD+ pathway," said Dr. Wakimoto, an Associate Professor of Neurosurgery at Harvard Medical School.

Dr. Miller, an Instructor in Neurology and a Neuro-Oncologist at Mass General who treats patients with IDH mutant glioma, noted that PAR glycohydrolase inhibitors are a newly-emerging class of drugs. "The long-term significance is that, based on our findings, they could be tested in individuals with IDH mutant gliomas, with a goal of hopefully improving outcomes in these patients," she said.
-end-


Massachusetts General Hospital

Related Chemotherapy Articles:

Chemotherapy is used to treat less than 25% of people with localized sarcoma
UCLA researchers have found that chemotherapy is not commonly used when treating adults with localized sarcoma, a rare type of cancer of the soft tissues or bone.
Starved cancer cells became more sensitive to chemotherapy
By preventing sugar uptake, researchers succeeded in increasing the cancer cells' sensitivity to chemotherapeutic treatment.
Vitamin D could help mitigate chemotherapy side effects
New findings by University of South Australia researchers reveal that Vitamin D could potentially mitigate chemotherapy-induced gastrointestinal mucositis and provide relief to cancer patients.
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.
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

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.