Cancer metastasis Archives - Sanford Burnham Prebys

Tag: Cancer metastasis

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How cancer cells change as they metastasize

AuthorScott LaFee
Date

December 9, 2024

cancer metastasis

Most cancer deaths are caused by metastasis, but how cancer cells and tumors modify themselves and spread from their origins to other parts of the body remains largely a mystery — and fundamentally challenging.

In a new paper published December 6, 2024 in Science Advances, study co-author Sanju Sinha, PhD, assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys, and colleagues, investigate whether primary and metastatic tumors more closely resemble the tissues of origin or target tissues in terms of gene expression.

Their findings suggest movement and evolution, providing a comprehensive transcriptome-wide view of the processes through which cancer tumors adapt to their metastatic environments before and after metastasis.

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Raising awareness of breast cancer research at Sanford Burnham Prebys

AuthorGreg Calhoun
Date

October 31, 2024

Kelly Kersten, PhD, and Kevin Tharp, PhD

The October Science Connect Series event was themed around Breast Cancer Awareness Month and featured two cancer research experts.

The Sanford Burnham Prebys Wellness Ambassadors hosted a Science Connect event on Wednesday, October 30, 2024, featuring two faculty experts discussing their breast cancer research and its implications.

The Science Connect Series provides a forum for Sanford Burnham Prebys principal investigators to share their research with administrative personnel. Faculty members gain experience in communicating their science to a lay audience, and administrators gain a better understanding of research conducted at the institute so they can become better advocates and ambassadors of the shared mission to translate science into health.

Kelly Kersten, PhD, an assistant professor in the Cancer Metabolism and Microenvironment Program, opened the event by focusing on the importance of finding new treatments —such as immunotherapies — for the one-third of breast cancer patients that are diagnosed after the early stages of the disease when surgery is less effective.

The immune system is one of the main defenses of the human body to fend off harmful pathogens and invasive cells, such as cancer. Among all white blood cells, a particular cell type, called a T cell, can directly kill cancer cells and therefore plays an essential role in building anti-tumor immune responses.

Many types of cancer are confronted and infiltrated by T cells, only to be suppressed by the local tumor environment.

“While immunotherapies that boost the immune system have revolutionized the way we treat cancer, many patients do not respond to the treatments, and the mechanisms of resistance remain largely unclear,” said Kersten.

Kersten’s goal is to understand why T cells enter a state known as exhaustion and lose their tumor-killing capacity. This knowledge will help her team find potential future therapies that could prevent T-cell exhaustion and improve immunotherapies for cancer patients.

Kevin Tharp, PhD, also an assistant professor in the Cancer Metabolism and Microenvironment Program, shared that his lab’s focus is on how cancer cells adapt their metabolism to generate the energy needed to spread to other tissues through metastasis. He presented his team’s work with the Kersten lab on another aspect of potential resistance to immunotherapy in breast cancer.

Tharp and Kersten are studying the hypothesis that part of the reason why these therapies fail is due to tumor-associated fibrosis, the creation of a thick layer of fibrous collagen (like scar tissue) that acts as a barrier against the anti-tumor immune response. They published a paper on June 3, 2024, in Nature Cancer,  discussing how tumor-associated macrophages, a type of immune cell found abundantly in the tumor microenvironment, respond to the physical properties of fibrosis.

By synthesizing injury-associated collagens that facilitate wound closure, TAMs experience metabolic changes and generate metabolic byproducts that suppress the anti-tumor function of immune cells.

“The metabolic changes in the microenvironment present more of a challenge to anti-tumor responses than the physical barrier,” said Tharp. “Our study provides an alternative explanation for why anti-tumor immunity is impaired in fibrotic solid tumors.”

To follow up on these results, Tharp is collaborating with Sarah Blair, MD, a professor of surgery at the University of California San Diego, to fund and initiate a clinical trial testing the potential of dietary supplements to counteract the suppressive effects of TAM metabolic byproducts as an adjunct therapy to surgery.

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Capturing circulating cancer cell clusters using a new microfluidic device

AuthorMonica May
Date

July 16, 2019

cancer cell clusters

Nearly 90 percent of cancer deaths are a result of metastases, when tumors spread to other vital organs. Researchers are learning that cancer metastases are not due to individual cells but rather distinct clusters of cancer cells that circulate and metastasize to other organs. However, obtaining these clusters to learn more about the metastatic process has proved difficult. 

Now, in a study published in AIP Advances, researchers from Sanford Burnham Prebys, San Diego State University and TumorGen MDx™ have described a new microfluidic device that captures circulating cancer cell clusters. 

“The reason for such little research activity on cancer clusters is the overwhelming difficulty of capturing these extremely rare samples from a patient’s blood sample,” says Peter Teriete, PhD, a study author and a research assistant professor at Sanford Burnham Prebys. “But we realized that if we’re ever going to understand the complex process of cancer metastasis, we’d need to develop a tool to easily find these clusters.”

To do so, the researchers first identified the basic requirements essential to collecting useful information from isolated cancer cell clusters. It involves a sample size large enough to likely contain appreciable numbers of cancer cell clusters (about 10 milliliters of whole blood), as well as using whole blood to preserve rare circulating clusters. Whole blood, however, requires special channel-coating procedures that reduce nonspecific binding properties to prevent biofouling. And the device channel dimensions must be of a suitable size to accommodate single cells and cancer cell clusters of varying diameters.

“Our device’s channel design had to generate microfluidic flow characteristics suitable to facilitate cell capture via antibodies within the coated channels,” Teriete explains. “So we introduced microfeatures—herringbone recesses—to produce the desired functionality. We also developed a unique alginate hydrogel coating that can be readily decorated with antibodies or other biomolecules. By connecting bioengineering with materials science and basic cancer biology, we were able to develop a device and prove that it performs as desired.”

The group’s microfluidic device brings a new therapeutic strategy to the fight against cancer metastasis. Capturing viable circulating cancer stem cell clusters directly from cancer patients is a novel approach for the development of new anti-metastatic drug therapies.

“Drug development that specifically targets distant metastases has been greatly restricted due to the lack of adequate tools that can readily access the metastatic cells responsible for cancer’s dissemination,” says Teriete. “Our microfluidic device will provide cancer researchers with actual human cancer cell clusters so they can begin to understand the critical mechanisms involved with metastasis and develop highly effective drugs that ultimately can save more cancer patients’ lives.”

Story materials courtesy of the American Institute of Physics. Content has been edited for style and length. 

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Hearst Foundation’s new fellowship funds innovative research to fight breast cancer

AuthorJessica Moore
Date

October 20, 2016

Charles Spruck, PhD, and Mark Goldberg, PhD

Mark Goldberg, PhD, is working on a potential way to turn cancer stem cells into harmless cells. He and his advisor, Charles Spruck, PhD, assistant professor in the NCI-designated Cancer Center, are optimistic that they could turn this approach into new drugs that prevent breast cancer from returning.

Goldberg is supported by the first-ever research fellowship given by the David Whitmire Hearst Jr. Foundation. The funds were awarded specifically for this groundbreaking project.

“Breast cancer can spread to other organs very early, sometimes even before it’s detected,” said Spruck. “Those micrometastases—just one or a few cells—lie dormant for years, and are insensitive to anticancer drugs. Our goal is to switch those cells to a normal cell type that can’t generate a tumor.”

In as-yet unpublished research, Spruck’s lab recently discovered a protein that’s crucial for pre-cancerous cells to begin growing aggressively and out of control. Goldberg will use animal models of breast cancer to show that genetically inactivating this protein prevents secondary tumors from forming. The next step is to search for candidate drugs that inhibit the protein.

“If we find blockers of this protein that controls progression to malignancy, they could be given to breast cancer patients, after standard treatment has eradicated their primary tumor, to eliminate any remaining cancer stem cells,” added Spruck.

Goldberg’s background in bioengineering gives him a fresh perspective on cancer research. As a PhD student at Caltech, he designed implantable glucose and ion sensors using microfluidics and nanophotonics. That experience gives him a flexible, solutions-oriented approach to designing experiments.

“During Mark’s interview—the first time I met him—we came up with a really exciting way to apply what he was working on at Caltech to cancer research,” Spruck commented. “That kind of creative thinking and insight is invaluable—it’s why I hired him for this fellowship-supported spot.

“Because this research is so early-stage, it’s hard to get funded through traditional avenues. The Hearst Foundation fellowship allows us to get the evidence that this strategy works. That data will be key to getting the support we need for the drug discovery phase.”