Nav: Home

UC San Diego cancer scientists identify new drug target for multiple tumor types

July 11, 2019

A research team headed by scientists at University of California San Diego School of Medicine and the Ludwig Institute for Cancer Research at UC San Diego has identified an enzyme involved in remodeling the plasma membrane of multiple cancer cell types that is critical to both survival of tumors and their uncontrolled growth.

The finding, published in the July 11, 2019 issue of Cell Metabolism, suggests a potential target for new drugs.

"Cancers are characterized not only by major changes in their genomes, but also by profound shifts in how they take up and utilize nutrients to propel rapid tumor growth," said senior author Paul S. Mischel, MD, professor in the UC San Diego School of Medicine Department of Pathology and Ludwig member. "How do these diverse aspects fit together and can they be taken advantage of, for the benefit of patients?"

In the new study, conducted in collaboration with Benjamin Cravatt, PhD, professor at Scripps Research, and led by first author Junfeng Bi, PhD, in Mischel's lab, researchers identified an enzyme called LPCAT1, whose levels increase in cancer and which plays a key role in tumor growth by changing the phospholipid composition of the cancer cells' plasma membrane, allowing amplified and mutated growth factor signals to spur tumor growth.

Without LPCAT1, tumors cannot survive. When researchers genetically depleted LPCAT1 in multiple types of cancer in mice, including highly lethal glioblastomas (brain) and an aggressive lung cancer, malignancies shrank dramatically and survival times improved.

The results, wrote the authors, demonstrate that LPCAT1 is an important enzyme that becomes dysregulated in cancer, linking common genetic alterations in tumors with changes in their metabolism to drive aggressive tumor growth."

"Advances in DNA sequencing technologies have reshaped our understanding of the molecular basis of cancer, suggesting a new and more effective way of treating cancer patients," said Mischel. "However, to date, precision oncology has yet to benefit many patients, motivating a deeper search into understanding how genetic alterations in tumors change the way cancer cells behave, and potentially unlocking new ways to more effectively treat patients.

"These results also suggest that LPCAT1 may be a very compelling new drug target in a wide variety of cancer types."
-end-
Co-authors include: Taka-Aki Ichu and Alex Reed, Skaggs Research; Ciro Zanca, Huijun Yang, Sudhir Chowdhry, Kristen M. Turner, Wenjing Zhang and Sihan Wu, Ludwig Institute for Cancer Research; Wei Zhang, Oswald Quehenberger, Jeremy N. Rich, Webster K. Cavenee and Frank B. Furnari, UC San Diego; Yuchao Gu and Genaro R. Villa, Ludwig and UCLA; Shiro Ikegami, Chiba University; William H. Yong, Harley I. Kornblum, and Timothy F. Cloughesy, UCLA.

Disclosure: Paul Mischel is co-founder of Pretzel Therapeutics. He has equity and serves as a consultant for the company. He also did one-time consultation for Abide Therapeutics.

University of California - San Diego

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".