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Gifts support efforts to understand and fight rare cancers

Treating cancer has been a dream of countless doctors and researchers for decades. However, some types of cancer receive less attention and funding than others, whether because they are affected by a relatively small number of people or have no influential supporters.

Rare cancer cells, known as precursor cell-like dendritic cell neoplasms, are shown in purple and blue and appear in red blood cells. Image: Clin Med Insights Case Rep 2013. doi: 10.4137 / CCRep.S12608, CC-BY-NC 3.0

A recent gift to Harvard Medical School is boosting efforts to understand and fight these under-studied malignancies.

Founded in 2019 at HMS by the Swiss-based Bertarelli Foundation, the Bertarelli Rare Cancer Fund provides $ 15 million to support rare cancer-focused research projects and community building.

The first round of grants was awarded, with more than $ 9 million distributed to nine teams representing 19 chief and co-principal researchers across HMS and its affiliated hospitals. The study began this winter.

“This exciting new program improves the ability to prevent, treat and treat rare cancers that affect tens of thousands of patients and their loved ones in the country each year,” said HMS Dean George Q. Daily. I am. “By building research capabilities and collaboration between organizations, this fund will help us pursue our mission to create new biological insights and therapeutic strategies that improve the health of all.”

We have a common ambition to research and innovate for society. Clearly, there is a need and opportunity to accelerate transformative rare cancer research, and we hope that the fund will work with scientists around the world to create a community of researchers who will transform understanding, treatment and care. hoping. Of rare cancer. “

Donna Bertarelli, Co-Chair of the Bertarelli Foundation

According to the National Cancer Institute, rare cancers, by definition, cause less than 40,000 US residents in a particular year, but about all cancers and cancer deaths in the country. It occupies a quarter.

Research on rare cancers can be difficult. For example, tissue samples are scarce and pharmaceutical companies have less incentive to develop medicines for the smaller patient market. Academic institutions such as HMS can be particularly helpful, according to Daily.

With new injections from the Bertarelli Foundation, HMS will be able to build infrastructure, generate knowledge and strengthen the rare cancer research community that will benefit from more common cancers.

This gift “spotlights rare cancer research needs” and “by supporting promising new research, attracting researchers and showing patients that they can make progress” some of those needs. Deal with. Professor of Cancer Research and Education at the Brabatonic Institute at DK Ludwig HMS.

The ultimate goal is to improve the detection, diagnosis, treatment and prevention of rare cancers.

“We want to provide concrete progress that will reduce the burden on patients and their families,” says Harlow.

The discoveries that emerge from the study of rare diseases can change science. William Kellin, HMS and Sidney Farber Medical Professor at the Dana-Farber Cancer Institute, shared the Nobel Prize in Physiology or Medicine in 2019 for the study of a rare tumor-driven disorder known as von Hippel-Lindau Syndrome. Insights on how cells sense oxygen. This has led to new treatments for anemia and has been shown to be associated with a variety of more common cancers.

In addition to the importance of understanding the basics of rare cancer and developing treatments, Bertarelli said: Rare diseases are important in many other diseases. “

Division and multiplication

The first grant spans basic science, translation science, and clinical science, connecting junior and senior faculty members throughout the HMS community. Interdisciplinary collaboration is committed to addressing issues from different perspectives and creating stronger science.

“A new eye on the results can open new angles, provide new insights, and discover missing parts,” Harlow said. “We encourage everyone to share advice and data before it’s published as an important part of building a useful community.”

Grant recipients are investigating genetic and molecular mechanisms that span multiple rare cancers, as well as a variety of individual rare cancers.

Nabeel Bardeesy, an associate professor at HMS and Massachusetts General Hospital, is studying a rare liver cancer in young adults known as fibrous stratified cancer. The fund allowed him to hire experts from various disciplines into the team.

He is currently investigating how changes in the genes that define this type of cancer affect tumor cells. Using genetics and proteomics, techniques that measure the levels of all proteins in cells, we reveal each gene and molecular circuit that promotes tumor growth. Search for cancer cell vulnerabilities that researchers can use to design drugs that attack.

“There was neither a critical mass of people studying fibrous layered cancer, nor a good toolkit of experimental model systems for exploring biology,” Bardeesy said. “This gift will allow us to move forward by addressing some of the biggest issues in the field, coming up with new approaches and strengthening the foundation of drug development that impacts patient care.”

Vamsi Mootha, a professor of systems biology at the Bravatnik Institute at HMS and a professor of medicine at Mass General, used a recently discovered class of cancer-driven genes to better understand Hürthle cell carcinoma, a rare cancer of the thyroid gland. I’m fighting. ..

Christopher French, an associate professor of pathology at HMS and Brigham and Women’s Hospital, focuses on the molecular interactions that cause NUT cancer, the most common aggressive cancer in the head, neck and lungs. Meanwhile, Andrew Lane, an associate professor of medicine at HMS, said Dana-Farber promotes uncontrolled cell division in cancers of precursor cell-like dendritic cell neoplasms, blood, bone marrow, and other tissues. The purpose is to clarify the essential proteins.

Gregor Mendel, a professor of genetics and medicine at HMS and Brigham and Women’s, takes a broader approach. His team seeks to develop a collection of all the abnormally fused genes known to play a role in rare cancers.

“These fusion oncogenes are not as well studied as other cancer driver genes,” Elledge said. “Although they are often found in rare cancers, some common cancers, such as prostate cancer, carry these fusion oncogenes in more than 50 percent of tumors.”

Researchers can then use any or all of the genes in Elledge’s collection to study the developmental process of specific or more universal cancers. The website tracks the relationships between fusion oncogenes and fusion-driven proteins and incorporates new discoveries when they become apparent.

Sink into problems

Some of the funded projects focus on clear cell cancers, especially rare types of under-researched cancers.

John Hannah, an assistant professor of pathology at HMS and Brigham and Womens, has sequenced the DNA and RNA of clear cell tumor samples. Many clear cell carcinomas look similar under a microscope, but genetic analysis allows for more subtle classifications that help doctors and researchers improve the diagnosis and prognosis of patients and provide more accurate treatments. Helps you develop.

It identifies a whole new type of clear cell tumor and other rare tumors that were previously unrecognized or were misconcentrated with other tumor types due to their similar appearance. Understanding specific molecular and genetic changes within a tumor will have a significant impact on our ability to care for patients. “

John Hannah, Pathology, HMS and Brigham and Female Associate Professor

Two projects led by Miguel Rivera, an associate professor of pathology at HMS and Massachusetts General Hospital, and Kimberly Stegmaier, a pediatric professor at HMS and Dana-Farber, on EWS fusion neoplastic proteins. I am investigating. Ewing’s sarcoma. Researchers plan to uncover how these fusion proteins work and test new ways to combat them.

“These cancers lacked effective targeted therapies because the fusion proteins were so difficult to fix,” says Stegmaier. “An interdisciplinary team of Ewing’s sarcoma and fusion neoplastic protein experts, chemists, and structural biologists will work together to address this issue using a new chemical approach that leverages the cells’ intrinsic protein processing mechanisms. I’m very excited about it. “

Stegmaier hopes that the model system the team is building to investigate EWS fusion proteins will help the broader research community to study other fusion-driven cancers.

Meanwhile, a team led by John Iaphrate, Austin L. Vickery, HMS and a professor of pathology at Massachusetts General Hospital aims to identify biomarkers that help detect and treat clear cell odontogenic cancer, tooth and jaw cancers. I have. , And related tissues, and use them to develop blood tests to track cancer during and after treatment.

Fund managers have biological tools for studying clear cell carcinoma, including cell lines, xenografts (tumor samples from patients studied in mice), mouse models, and three-dimensional tissue structures known as organoids. We will support additional projects to build.

Harlow and the team are seeking additional funding to expand the program and gain more community momentum in rare cancer studies.

The Bertarelli Rare Cancers Fund complements the Bertarelli program of translational neuroscience and neural engineering to support “bench-to-bedside” research at HMS.

Gifts support efforts to understand and fight rare cancers

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