, a state research agency administered by the 

 is providing $3.7 million in funding to operate the center for four years.

“Tobacco use is linked to 30% of all cancer-related deaths and it gets in the way of achieving health equity,” said UC Davis Comprehensive Cancer Center Director 

“That’s why the new tobacco center aligns so well with our mission and the diverse population we serve. We anticipate that the center will deliver local and regional tobacco control policies, which in turn will result in broad statewide and national impact.”

, a nationally recognized tobacco researcher and an internist at 

, will serve as the center’s director. Tong is medical director of the UC Davis Comprehensive Cancer Center 

. She is also principal investigator for 

 managed care plans and providers to improve tobacco treatment delivery.

“The mission of our center is to build capacity for health care access, promote excellence in health care delivery, facilitate health care and community engagement, and achieve equity in health plan coverage,” Tong said. “Our center will generate evidence for policy adoption and implementation, collaborate with community and policy stakeholders, and develop the pipeline of researchers to sustain the mission.”

American Cancer Society Cancer Action Network

, a UC systemwide program for public policy teaching, research and public service. Both the cancer center and ACS CAN have a history of working throughout Northern and Central California and are members of the 

Greater Sacramento Smoke & Tobacco-Free Coalition

, an important foundation of community collaboration.

“Public health has claimed important victories in California with the implementation of strong local and state tobacco control policies, including ending the sale of menthol cigarettes and all other flavored tobacco products,” said Jen Grand-Lejano, ACS CAN senior government relations director for Northern California and grant program. “As we move forward in reducing suffering and death from tobacco-related diseases (such as cancer), we must continue to ensure Californians who use tobacco have access to comprehensive and barrier-free services to help them quit.”

“This new center has the potential to significantly reduce tobacco-related harm in our state. As the University of California’s main hub for policy-related knowledge sharing in the state capital, we are proud to participate in advancing the training and dissemination aims of this grant,” said Richard L. Kravitz, director of UC Center Sacramento.

“Policy changes have great potential to increase tobacco cessation in California, which in turn will reduce overall and disparities in tobacco-related diseases. This new center is an important statewide effort by multiple University of California campuses to reduce one of the leading causes of morbidity and mortality in California,” said UCLA Health’s Michael Ong, who is chair of the 

State of California Tobacco Education and Research Oversight Committee

Advancing tobacco cessation policy research

The new center will deploy four “rapid response” policy projects that will address key areas for current and future legislative policies for tobacco cessation:

. Community pharmacies are important points of health care access and California pharmacists can furnish nicotine replacement therapy without a prescription. This study will examine barriers to implementing 

. Enacted in 2016, the law allows Medi-Cal plans to reimburse community pharmacists affiliated with 

Community Pharmacy Enhanced Services Network

. People with substance use disorders have high rates of tobacco use but people in treatment facilities don’t always get the help they need to quit. This study will examine barriers to implementing 

 (enacted in 2021) for substance use disorder facilities to conduct tobacco status assessments and treatments.

 (effective January 1, 2023) bans the retail sale of most flavored tobacco products and is an opportunity for people to quit menthol and other flavors in e-cigarettes. This study will examine a strategy to engage health care providers on local policy adoption and implementation.

 Comprehensive tobacco treatment coverage is in place for Medi-Cal but not for other publicly covered health plans, such as those for state employees. Two attempts at legislation to accomplish this have failed. Research can help define health economic scenarios for policy decision makers.

“Study findings will support efforts to expand into subsequent studies or generate new policy efforts,” Tong said. “The long-term impact is to improve population-based cessation outcomes that will help fulfill California’s aspirations of an 

 to end the commercial tobacco epidemic and help save lives.”

Articles

UC Davis Comprehensive Cancer Center has launched the state’s first-ever Tobacco Cessation Policy Research Center. 

New California Tobacco Cessation Policy Research Center to be Housed at Cancer Center

Gene therapy that induces the body to create microRNA-22 (miR-22), a naturally occurring molecule, successfully treated mice with hepatocellular carcinoma, the most common form of liver cancer.

The miR-22 treatment also reduced liver inflammation and produced better survival outcomes with no observable toxicity compared to the FDA-approved liver cancer treatment 

“This research introduces miR-22 gene therapy as a promising and innovative approach for treating hepatocellular carcinoma,” said 

, senior author of the study. Wan is a distinguished professor and vice chair for research in the UC Davis 

Department of Pathology and Laboratory Medicine

. “The study's findings suggest that miR-22 therapy could provide better survival outcomes, enhance anti-tumor immunity, improve metabolism and reduce inflammation.”

 for Wan’s discovery of miR-22 for treating hepatic and metabolic diseases. The patent is currently pending.

 (RNA), a type of genetic material. MicroRNAs are widely found in plants and animals. They are “non-coding,” meaning they do not make proteins like some other RNA molecules.

In the case of miR-22, it acts like a brake, stopping the production of certain proteins, including 

, that can fuel liver cancer growth. A lack of miR-22 is found in hepatocellular carcinoma tumors, and its levels can predict survival time for patients with the disease.

Wan studies the interaction between gut microbes and the liver, what’s known as the gut-liver axis. 

 shows that metabolites produced by the gut microbiome help create miR-22 and have anti-cancer benefits. These metabolites include 

When people have colon or liver cancer, signaling from these metabolites is reduced, which in turn reduces miR-22.

This was a clue for Wan that returning miR-22 to a higher level might act as a treatment for liver cancer. She launched several studies, including one demonstrating miR-22 could 

 by targeting both liver and immune cells.

Gene Therapy to Test Efficacy of miR-22 for Liver Cancer

, an assistant professional researcher in Wan’s lab, turned to 

Using an inactivated adenovirus, they introduced miR-22 into mice with a single intravenous injection.

The mice treated with the gene therapy were compared with mice treated with the current FDA-approved drug 

 (administered orally once a day), untreated mice and healthy mice.

Both miR-22 and lenvatinib inhibited the progression of the liver cancer compared to untreated mice. However, the miR-22-treated mice had longer survival times without toxicity compared with lenvatinib-treated mice. Some of the study’s key findings:

MiR-22 and lenvatinib reduced serum alanine transaminase (

MiR-22-treated mice showed no blood or organ toxicity.

At five weeks, untreated mice had enlarged livers, making up 33.5% of their body weight. The treated mice had smaller, less diseased livers, with ratios of 10.9% (miR-22) and 12.0% (lenvatinib) of body weight.

The median survival rate was 46 days for the lenvatinib group and 50 days for the miR-22 group.

Two mice treated with miR-22 remained alive for 60 days. In contrast, the survival time for the untreated mice was about 40 days.

Liver Cancer is a Leading Cause of Death Worldwide

 worldwide, accounting for more than 700,000 deaths each year. 

 are diagnosed with liver cancer, while 19,000 men and 9,000 women die from the disease.

 (a toxin found in moldy peanuts or grains).

Hepatocellular carcinoma is becoming a bigger problem due to rising obesity rates worldwide, including in the U.S.

Drugs to treat hepatocellular carcinoma — 

 — are associated with considerable toxicities and poor quality-of-life outcomes. The survival benefit is limited to a few months and the cost is very high.

“The positive findings from this preclinical study give us hope that miR-22 could be a promising alternative to treat hepatocellular carcinoma,” Hu said.

Additional authors include Tahereh Setayesh, Farzam Vaziri, Xuesong Wu and Samuel T. Hwang from UC Davis.

Research for this study was funded by National Institutes of Health grants R01CA222490, R50CA243787 and T32 CA108459-15.

Centers for Disease Control and Prevention: Liver cancer

Previous miR-22 Research From the Wan Lab

MiR-22-silenced cyclin A expression in colon and liver cancer cells is regulated by bile acid receptor

RARβ acts as both an upstream regulator and downstream effector of miR-22, which epigenetically regulates NUR77 to induce apoptosis of colon cancer cells

Gene therapy that induces the body to create microRNA-22, a naturally occurring molecule, successfully treated mice with hepatocellular carcinoma, the most common form of liver cancer.

Gene Therapy Study Identifies Potential New Treatment for Liver Cancer

 is the second leading cause of death in American men. Understanding the factors that influence patient outcomes is critical for improving treatment and survival rates.

 reveals a link between bone metabolism biomarkers and survival in men with newly diagnosed 

 Phase 3 trial of nearly 1,000 patients on ADT, including some who were also on the novel hormonal therapy 

. Patients participating in the trial came from 248 academic and community centers throughout the country.

Bone biomarkers for both bone loss and bone formation were measured in HSPC patients enrolled in the trial.

The researchers found that elevated bone biomarkers were associated with an increased risk of death. Bone biomarkers have been found to influence overall survival in men with 

(CRPC), but have not been fully established for HSPC. CRPC is a prostate cancer that continues to grow even when testosterone levels are greatly reduced.

“Our findings show that high levels of bone turnover biomarkers are associated with a shorter lifespan in men newly diagnosed with metastatic HSPC,” said UC Davis Comprehensive Cancer Center Director 

 “In the future, knowing one’s bone biomarker status could improve how we predict patient outcomes and enhance treatment considerations for men with HSPC.”

Managing bone health during prostate cancer treatment

A finely balanced interaction between cells that rebuild bone and cells that destroy bone is common in men with advanced prostate cancer. These men often present with skeletal metastasis, a common source of bone pain and fracture that can affect their survival.

In addition, men with metastatic HSPC are typically treated with ADT, which disrupts bone turnover and contributes to the development of bone diseases such as 

. Previous studies have shown that elevated levels of blood-based biomarkers of bone turnover predict survival in men with CRPC and bone targeted therapy may help patients with highly elevated markers.

“This study takes a similar look at bone turnover biomarkers in men with advanced or metastatic HSPC who are initiating ADT as part of a large phase 3 clinical trial,” said co-author and UC Davis Comprehensive Cancer Center clinical scientist 

. She is also the cancer center’s director of genitourinary malignancies. “Ultimately, our findings add to the growing understanding of the complex interplay between cancer and bone metabolism, which will also help us design of future clinical trials.”

Other contributors to the study included Edward Mayerson, Catherine Tangen and Michael LeBlanc from the SWOG Statistical Center, Seattle; Erik Gertz and Marta van Loan from the U.S. Department of Agriculture, Western Human Nutrition Research Center, Davis; Amir Goldkorn and David I. Quinn from the USC Norris Comprehensive Cancer Center, Los Angeles; Maha Hussain with the Northwestern University, Chicago; Shilpa Gupta with the Cleveland Clinic, Cleveland; Jingsong Zhang with Moffit Cancer Institute, Tampa Bay; Przemyslaw Twardowski with St. John’s Cancer Institute, Providence Health, Santa Monica; Nicholas J. Vogelzang with Comprehensive Cancer Centers of Nevada, Las Vegas; Ian Thompson with Christus Santa Rosa Health System, TX Health, San Antonio and Neeraj Agarwal with Huntsman Cancer Institute, Salt Lake City.

New study led by UC Davis Comprehensive Cancer Center could improve outcomes for common cancer found in 1 in 8 men.

Strong Link Between Bone Biomarkers and Prostate Cancer Survival

 has launched a Center for Experimental Therapeutics in Cancer to accelerate promising cancer therapies from the lab to the bedside. The goal is to facilitate the commercialization of promising drugs emerging from UC Davis laboratories by establishing a hub for the development of startups and the acquisition of small business grant funding from the 

“We see the Center for Experimental Therapeutics in Cancer as an incubator for bringing multidisciplinary teams from throughout UC Davis together with biotech and pharmaceutical companies working hard to move anti-cancer agents through the drug development pipeline, from start to finish,” Lam said.

The idea is to advance more effective, less toxic cancer therapies to meet the demand for precision medicine. These treatments target individual patients with care customized to specific cancer biomarkers, using the latest biological therapies and drug agents.

“The next frontier has arrived and we are poised to accelerate the discovery of novel cancer treatments based on a genetic understanding of a patient’s cancer,” said UC Davis Comprehensive Cancer Center Director Primo “Lucky” Lara Jr. “Rather than a one-drug-fits-all approach, precision medicine is leveraging novel pathways, biomarkers and other discoveries, which we want to coordinate through this new center, designed to translate research quickly into clinical settings.”

The center will facilitate close collaboration with basic researchers, clinicians and translational scientists, including launching clinical trials to evaluate these newly identified anti-cancer agents. Researchers will work with pharma and biotech companies, venture capitalists, nonprofit foundations and academia, as well as the National Institutes of Health and National Cancer Institute.

In addition to rendering scientific and technical assistance, the Center for Experimental Therapeutics in Cancer will offer support for drug development by means of the Food and Drug Administration’s Investigational New Drug application process. The new center additionally will facilitate communication with UC Davis experts in intellectual property, licensing and patents.

“We also want to ensure ongoing educational opportunities such as workshops and symposiums in addition to helping advance the careers of researchers who come from underserved communities,” Gandara said. “We are committed to working with our 

Office of Community Outreach and Engagement

 to ensure that the research taking place also addresses cancer health disparities in our region.”

Center will serve as a hub for commercialization of promising cancer therapies.

New Center for Experimental Therapeutics in Cancer Advances Promising Treatments

A new UC Davis-led study sheds light on cell type-specific biomarkers, or signs, of 

. The research was recently published in the 

Melanoma, the deadliest of the common skin cancers, is curable with early diagnosis and treatment. However, diagnosing melanoma clinically and under the microscope can be complicated by what are called 

—otherwise known as birth marks or moles that are non-cancerous. The development of melanoma is a multi-step process where “melanocytes,” or the cells in the skin that contain melanin, mutate and proliferate. Properly identifying melanoma at an early stage is critical for improved survival.

“The biomarkers of early melanoma evolution and their origin within the tumor and its microenvironment are a potential key to early diagnosis of melanoma,” said corresponding author of the study 

, associate professor of clinical dermatology and pathology at 

. “To unravel the mystery, we used high-plex spatial RNA profiling to capture distinct gene expression patterns across cell types during melanoma development. This approach allows studying the expression of hundreds or thousands of genes without disrupting the native architecture of the tumor.”

"The biomarkers of early melanoma evolution and their origin within the tumor and its microenvironment are a potential key to early diagnosis of melanoma," said Maija Kiuru, UC Davis melanoma researcher.

The study examined the expression of over 1,000 genes in 134 regions of interest enriched for melanocytes, a cell in the skin and eyes that produces the pigment called melanin, as well as neighboring keratinocytes or immune cells. The tissue examined came from patient biopsies from 12 tumors, ranging from benign to malignant, using the 

NanoString GeoMx® Digital Spatial Profiler

“We found that melanoma biomarkers are expressed by specific cell types, some by the tumor cells but others by neighboring cells in the so-called tumor microenvironment. The most striking observation was that 

, which is a known melanoma marker thought to be expressed by immune cells, was expressed by keratinocytes that make up the outermost layer of the skin called the epidermis,” said Kiuru. “Melanoma biomarkers in the epidermis have been largely overlooked in the past.”

 that have multiple functions, including forming a barrier against micro-organisms, heat, water loss, and ultraviolet radiation. Normal keratinocytes also control the growth of melanocytes. 

 is expressed by keratinocytes within the tumor microenvironment during melanoma growth,” said Kiuru. “We further looked at 

expression in 252 benign and malignant melanocytic tumors, which showed prominent keratinocyte-derived 

 expression in melanoma but not in benign tumors. This suggests that 

 expression in the epidermis may be a readily detectable indicator of melanoma development.”

Many molecular tests for diagnosis and prognosis of melanoma are gradually being introduced but markers of early melanoma development, particularly in the tumor microenvironment, remain lacking. In addition, although the treatment of metastatic melanoma has changed drastically since the development of immune checkpoint inhibitor therapies, biomarkers predicting the duration a patient will be cancer-free are largely unknown. Previous research has utilized sophisticated methods, including single-cell RNA sequencing, but has largely focused on melanoma metastases, or secondary tumor growths. This has overlooked the keratinocyte microenvironment of primary melanomas.

Other authors of the study include Michelle A. Kriner, Nanostring Technologies; Samantha Wong, UC Davis; Guannan Zhu, UC Davis and Xijing Hospital; Jessica R. Terrell, UC Davis; Qian Li, UC Davis; Margaret Hoang, Nanostring Technologies; Joseph Beechem, Nanostring Technologies; John D. McPherson, UC Davis.

National Institute of Arthritis and Musculoskeletal and Skin Diseases

, which is part of the National Institutes of Health (grant #K23AR074530) and 

Career Development Award in Dermatopathology

UC Davis cancer researchers hope new technology will help diagnose and treat melanoma more successfully.

UC Davis Health

Articles

New California Tobacco Cessation Policy Research Center to be Housed at Cancer Center

Gene Therapy Study Identifies Potential New Treatment for Liver Cancer

Strong Link Between Bone Biomarkers and Prostate Cancer Survival

New Center for Experimental Therapeutics in Cancer Advances Promising Treatments

New Gene Profiling Technology Reveals Melanoma Biomarkers