Chadley Uekman

Pebbles Fagan, Ph.D., MPH

What is your relationship to cancer?

I am a member of the Winthrop P. Rockefeller Cancer Institute’s Cancer Prevention and Population Sciences Research Group and conduct tobacco prevention and control and colorectal cancer screening research.

Why this research interest?

My entire family on my maternal grandmother’s side has been impacted by cancer. Most of my grandmother’s brothers and sisters died of some type of cancer. My maternal grandmother died prematurely of breast cancer. She did not tell anyone that she had cancer because she thought cancer was a death sentence. I wanted to do something to prevent my family and community members from dying prematurely from cancer. Tobacco use is 100% preventable. Lung cancer is about 90% preventable because 90% of all lung cancers are caused by tobacco use and exposure to secondhand smoke.

What do you hope to contribute through your research to the Cancer Institute?

My goal is to reduce the disproportionate burden of cancer on African Americans and residents in rural areas.

Tell us about your current research?

My current research aims to identify effective strategies to reduce secondhand smoke exposure, help smokers quit, and reduce menthol and flavored tobacco use among racialized groups, young people, women and marginalized groups. I spend quite a bit of time conducting community-based research and tobacco regulatory science research. My regulatory science research seeks to influence policy change at the federal level. My goal is the reduce the toll of tobacco-caused cancers among groups who experience health and social disparities.

View Dr. Fagan’s Directory Profile
Brief Biography

UAMS Receives $18.9 Million NIH Award to Address Health Disparities

3D Prediction of Patient-Specific Response (3D-PREDICT)

News Release

3D-PREDICT is a prospective, open-label, non-interventional study to validate KIYATEC’s ovarian cancer drug response profile, which leverages the company’s ex vivo 3D cell culture technology platform to assess pre-treatment, patient-specific response to a panel of 11 drugs most commonly used to treat patients with newly diagnosed or recurrent ovarian cancer.

Details on the study can be found at
https://clinicaltrials.gov/ct2/show/NCT03561207.

“The Winthrop P. Rockefeller Cancer Institute is proud to offer 3D-PREDICT to our ovarian cancer patients. It is our hope that this trial will help develop a method to assist us in determining which drugs will most benefit individual patients and get them on the most effective treatment as quickly as possible,” said Michael Birrer, M.D., Ph.D., vice chancellor and director of the Cancer Institute.

KIYATEC leverages its proprietary ex vivo 3D cell culture technology platforms to accurately model and predict response to approved and investigational cancer drugs targeting a spectrum of solid tumors. The company’s Clinical Services business is currently engaged in the validation of clinical assays as well as investigator-initiated studies in ovarian cancer, breast cancer, glioblastoma and rare tumors, in its CLIA-certified laboratory. The company’s Drug Development Services business works in partnership with leading biopharmaceutical companies to unlock response dynamics for their investigational drug candidates across the majority of solid tumor types.

Lung-MAP: A Master Screening Protocol for Previously-Treated Non-Small Cell Lung Cancer

This screening and multi-sub-study randomized phase II/III trial will establish a method for genomic screening of similar large cancer populations followed by assigning and accruing simultaneously to a multi-sub-study hybrid Master Protocol (Lung-MAP). The type of cancer trait (biomarker) will determine to which sub-study, within this protocol, a participant will be assigned to compare new targeted cancer therapy, designed to block the growth and spread of cancer, or combinations to standard of care therapy with the ultimate goal of being able to approve new targeted therapies in this setting. In addition, the protocol includes non-match sub-studies which will include all screened patients not eligible for any of the biomarker-driven sub-studies.

Learn more at clinicaltrials.gov

Cancer by Seymour Berger

Cancer will be the word of the past
Our researchers will find a cure that will last
Never give up any hope, always look ahead
Things that are changing is going to make cancer dead
Countless of people with this horrible disease
For the light that cast upon them, they shall be please
Never think for a second your life is over
Your life is, in the hands of the beholder
For the scientist are like an instrument in God’s hands
They have a gift to make everyone well as it stands
To make them healthy from this aliment
In all the time they have spent
They will develop a miracle pill
No matter what stage you’re in, it will kill
Don’t get discourage, have faith
You will see it’s worth the wait
Your doctor will call and say it’s here
That miracle pill has arrived that will make cancer disappear
I dedicate this poem to everyone who has cancer, don’t become sadden
Many are cured you’re next and it will happen
My wife has lung cancer, no matter what the doctor, may say
Reading different articles the cure for all cancers its on its way
Never give up and say you’re done
Have faith always you will be the happy winning one

Can immune therapy help extend the life of people with a glioblastoma (brain tumor)?

NRG Oncology Clinical Trial: NRG-BN007

Protocol NRG-BN007, A Randomized Phase II/III Open-Label Study of Ipilimumab and Nivolumab Versus Temozolomide in Patients With Newly Diagnosed MGMT (Tumor O-6-Methylguanine DNA Methyltransferase) Unmethylated Glioblastoma (NCT 04396860)

Can immune therapy help extend the life of people with a glioblastoma (brain tumor)?

About the trial

NRG-BN007 is a clinical study that replaces the usual treatment of chemotherapy with immune therapy treatment for people who have a type of brain tumor called a glioblastoma and a tumor biomarker called “not methylated” or “unmethylated” MGMT. A biomarker is a change in the tumor’s genes that gives information about how the tumor may respond to treatment. Typically, people with this type of brain tumor undergo surgery to remove the tumor followed by radiation therapy and a Food and Drug Administration (FDA)-approved chemotherapy drug called temozolomide. Additionally, some patients also use an FDA approved wearable device called Optune to accompany the usual treatment, which uses electrodes applied to the patient’s head to send electric signals that could slow or stop cancer cell growth. NRG-BN007 was designed to determine if replacing the chemotherapy drug temozolomide with the immune therapy drugs ipilimumab and nivolumab can help lengthen the time without the brain tumor growing or returning and extend the life of patients who have a glioblastoma when compared to the usual treatment approach. Immune therapy drugs, or immunotherapy, stimulate or suppress the immune system to allow the body to fight the cancer.

About NRG Oncology

As one of the five research groups in the National Cancer Institute’s (NCI) National Clinical Trials Network (NCTN), NRG Oncology carries out clinical trials on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization includes investigators, medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians. The NRG Oncology includes more than 1,300 research sites worldwide, primarily in the United States and Canada. NRG Oncology is a non-profit research organization, funded mainly through grants from the NCI.

To contact NRG Oncology, call 267-519-6630 or email info@nrgoncology.org.

Frequently Asked Questions

What is a clinical trial?

Clinical trials are research studies that look to find better ways to prevent, diagnose, or treat disease.

Who can join this study?

Men and women 18 and older who have a glioblastoma that has the unmethylated MGMT biomarker and who have not yet received treatment.

Am I required to be in this study?

No. Taking part in this study is voluntary. You are free to choose to participate or not to participate. If you choose to participate in this study, you are able to leave the study at any time. If you decide not to take part in this study, your doctor will discuss other treatment options with you.

What are the possible study treatments?

If you decide to take part in the study, you will be assigned by chance to one of two treatment groups.

Patients assigned to group one will get the usual treatment approach of radiation therapy combined with temozolomide chemotherapy followed by further temozolomide chemotherapy when the radiotherapy treatment ends. Patients in group one also have the option of using the Optune device. Patients assigned to group two will receive radiation therapy combined with the immune therapy drugs ipilimumab and nivolumab. Patients in group two will continue to receive the immune therapy drugs when the radiation treatment ends.

How long will I be in this study?

If you are assigned to group one, you will receive chemotherapy every day for approximately 6 weeks and, during this time, you will also receive radiation therapy 5 days per week for the 6 weeks. Beginning 1 month following radiation therapy, you will receive chemotherapy 5 days in a row every 4 weeks for up to 12 months. Temozolomide, the chemotherapy drug, will be taken by mouth.

If you are assigned to group two, you will receive radiation therapy 5 days per week for 6 weeks plus the immune therapy drug ipilimumab by vein every 4 weeks for 4 times and nivolumab by vein every 2 weeks. Both ipilimumab and nivolumab treatment will start the first day you start radiotherapy. You will continue to receive nivolumab every 2 weeks for as long as you seem to benefit from it.

After you finish your treatment, your doctor and study team will watch you for side effects and continue to evaluate your disease.

Are there side effects?

There may be some. The radiation therapy treatment and chemotherapy and immune therapy drugs used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. Some common side effects of the chemotherapy drug used in this study include headaches, trouble with memory, nausea or vomiting, muscle weakness, difficulty sleeping, and more. A common side effect of nivolumab is tiredness. Some common side effects of ipilimumab include skin problems such as itching, rash, hives, and blisters, tiredness, diarrhea, nausea, and more. Some common side effects of radiation therapy to the brain include hair loss, reddening of the skin, tiredness, lethargy, and more. Your doctor will review all of the potential side effects with you.

More Information

Visit the National Cancer Institute website at www.cancer.gov for more information about studies or general information about cancer. You may also call: 1-(800)-4-CANCER (1-800-422-6237).

Findings on DNA Damage Repair Published By UAMS Cancer Researcher

A UAMS research team led by Justin Leung, Ph.D., (pictured front) was published in the journal Nature Communications. Co-authors of the study are Jessica Kelliher, B.S., (left) and Kirk West, Ph.D.

Findings on DNA Damage Repair Published by UAMS Cancer Researcher

By Susan Van Dusen

June 3, 2020 | LITTLE ROCK — A research team led by cancer researcher Justin Leung, Ph.D., at the University of Arkansas for Medical Sciences (UAMS) has uncovered the role of the protein RNF168 in DNA damage repair and shown how mutations of the protein affect people with a rare genetic condition.

The study titled “Histone H2A variants alpha1-extension helix directs RNF168-mediated ubiquitination” was published in the May 18 issue of the open-access journal Nature Communications.

“Every day our cells are subjected to environmental sources of DNA damage, such as ultraviolet radiation and toxic chemical exposure. If left unrepaired, these damages can accumulate, leaving mutations in our DNA and ultimately cause cells to become cancerous,” said Leung, assistant professor in the UAMS College of Medicine Department of Radiation Oncology.

In most cases, this damage is detected and repaired by a tightly regulated method involving many proteins. To develop better cancer therapies, researchers such as Leung strive to understand the regulation of DNA damage and repair by sensitizing cells to radiation therapy and chemotherapy drugs that target DNA.

“Our lab studies the repair of double stranded breaks, where both strands of DNA are broken apart completely. When a double strand break occurs, a cascade of protein activity is set off to try to resolve the damage,” Leung said.

Mutations in one of these proteins, RNF168, have been found in patients with RIDDLE syndrome, a rare genetic disorder that increases a person’s predisposition to blood cancer and is characterized by several attributes:

Susceptibility to DNA damaging agents
Immunodeficiency, or failure of the immune system to protect the body from infection
Developmental abnormalities
Learning disabilities

RNF168 adds a small signaling molecule called ubiquitin onto a subunit of chromatin, where we store our genetic information. The ubiquitin signal brings repair proteins to DNA double strand breaks. However, exactly how RNF168 recognizes the specific target remains unclear.

Using molecular and structural analysis methods, Leung’s team uncovered crucial components of RNF168 and chromatin required for the implementation of repair pathways in response to DNA damage. Their findings suggest that a recognition between RNF168 and chromatin is required to activate the downstream DNA repair processes.

“RNF168 is a central DNA damage response protein. Understanding the precise mechanisms by which it activates its targets is essential for understanding how the DNA damage response goes awry. Our results help demystify the role of RNF168 in proper DNA damage repair and understand the implications of RNF168 mutations such as those seen in RIDDLE syndrome,” Leung said.

UAMS authors for this study included Jessica Kelliher, B.S., research assistant, and Kirk West, Ph.D., postdoctoral fellow.

UAMS is the state’s only health sciences university, with colleges of Medicine, Nursing, Pharmacy, Health Professions and Public Health; a graduate school; a hospital; a main campus in Little Rock; a Northwest Arkansas regional campus in Fayetteville; a statewide network of regional campuses; and eight institutes: the Winthrop P. Rockefeller Cancer Institute, Jackson T. Stephens Spine & Neurosciences Institute, Harvey & Bernice Jones Eye Institute, Psychiatric Research Institute, Donald W. Reynolds Institute on Aging, Translational Research Institute, Institute for Digital Health & Innovation and the Institute for Community Health Innovation. UAMS includes UAMS Health, a statewide health system that encompasses all of UAMS’ clinical enterprise. UAMS is the only adult Level 1 trauma center in the state. UAMS has 3,485 students, 915 medical residents and fellows, and seven dental residents. It is the state’s largest public employer with more than 11,000 employees, including 1,200 physicians who provide care to patients at UAMS, its regional campuses, Arkansas Children’s, the VA Medical Center and Baptist Health. Visit www.uams.edu or uamshealth.com. Find us on Facebook, X (formerly Twitter), YouTube or Instagram.

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UAMS Winthrop P. Rockefeller Cancer Institute To Host ‘Be a Part of the Cure’ Sept. 2 on KATV

Be a Part of the Cure, UAMS Winthrop P. Rockefeller Cancer Institute

UAMS Winthrop P. Rockefeller Cancer Institute To Host ‘Be a Part of the Cure’ Sept. 2 on KATV

By Susan Van Dusen

June 1, 2020 | LITTLE ROCK — Arkansans are invited to “Be a Part of the Cure” on Sept. 2 when the Winthrop P. Rockefeller Cancer Institute at the University of Arkansas for Medical Sciences (UAMS) hosts its first-ever televised event to raise funds and awareness for its research and treatment programs.

The event is set for 11 a.m. – 6:30 p.m. Sept. 2 on KATV, Channel 7, and will allow Cancer Institute supporters to phone or text their donations in support of the institute’s programs. Natalie and Win Rockefeller Jr. are the event chairs.

Members of the Cancer Institute’s Board of Advisors, along with other supporters and local celebrities, will answer phones throughout the event, which will air live on KATV periodically throughout the day.

To make a donation prior to Sept. 2, visit the Be a Part of the Cure webpage.

Individuals also are invited to share stories and photos about their cancer experience and how the Cancer Institute impacted their lives by visiting the Cancer Institute’s Facebook page.

“The lives of Arkansans are saved every day thanks to the world-class doctors, nurses and scientists at the Winthrop P. Rockefeller Cancer Institute. Unfortunately, however, we are still far from finding cures for many types of cancer,” said Win Rockefeller.

“That’s why,” added Natalie Rockefeller, “we are proud to give every Arkansan the chance to support the Cancer Institute safely from the comfort of their own home.”

The Cancer Institute’s 25^th Anniversary Gala for Life, originally scheduled for Oct. 2, has been postponed until 2021 due to safety measures related to COVID-19.

“We are grateful to Natalie and Win Rockefeller Jr. for working tirelessly to ensure that the Cancer Institute’s research and treatment programs can continue to thrive and benefit all Arkansans, especially during these challenging times,” said Michael Birrer, M.D., Ph.D., vice chancellor and director of the Cancer Institute.

Viewers also will learn about the institute’s quest to achieve National Cancer Institute (NCI) Designation, which is awarded through a highly competitive assessment process. To achieve designation, cancer centers must demonstrate outstanding depth and breadth of high-quality cancer research, including basic laboratory, patient/clinical and population-based research.

Achieving NCI Designation would provide many tangible benefits, including improved access to clinical trials and new therapies unavailable elsewhere in the state; greatly increased access to federal research grant awards; and the creation of more than 1,500 new jobs over five years.

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Head and Neck Cancer Vaccine Trial

This current study has been designed to evaluate the safety and efficacy of giving seven injections of PepCan or placebo over approximately a 24-month period in subjects with head and neck cancers who achieved remission. PepCan may prove to be beneficial in treating many stages of HPV-related malignancies starting from infection to cancer. Safety, efficacy in terms of reduced cancer recurrence, immunological responses and profiles, and gut microbiome changes will be assessed.

Learn more about this trial at clinicaltrials.gov

Developmental Therapeutics Research Program Highly Collaborative and Translational

The Developmental Therapeutics program at the UAMS Winthrop P. Rockefeller Cancer Institute focuses on developing hypotheses and evidence-based translational strategies for improved cancer treatment.

Hong-yu Li, Ph.D., professor in the UAMS College of Pharmacy Department of Pharmaceutical Sciences, serves as program leader.

The Cancer Institute’s largest research program, Developmental Therapeutics was originally known as the Therapeutic Science program. It recently received a name change and more focused mission emphasizing technology associated with the discovery and development of small molecule drug agents and biological therapies. This discovery phase is followed by validation using preclinical and clinical models.

“Our focus is both highly translational and highly collaborative. If we want to achieve results, we must collaborate with others, not only in this program, but also across UAMS, nationally and internationally. Collaboration is a priority in our success,” Li said.

The program’s main goals emphasize the optimization of therapies that connect the bench to the bedside through the discovery and development of new drugs for new cancer targets. By establishing a Phase 1 Clinical Trial Unit at the Cancer Institute, scientists could directly connect patient outcomes to their preclinical studies.

“A Phase 1 Unit would allow us not only to take our discoveries from bench to bedside, but also from the bedside back to the bench. If we found new mutations or biological targets, we can go back to the bench and continue working on those to further develop and improve the new drugs,” Li said.

Ultimately, the program aims for its members and collaborators to translate their research into new drugs for the marketplace. This directly ties to the Cancer Institute’s quest for National Cancer Institute (NCI) Designation, as NCI requires evidence of patents received and companies formed based on research accomplished at the centers.

The fact that program members have a wide range of expertise and practical experience in developing Investigational New Drug (IND) applications and conducting IND studies and clinical trials, gives the program an advantage.

“NCI wants to see us translate our basic research into something useful for the public. That, of course, is our ultimate goal as well,” Li said.

Cancer Biology Research Program Aims to Understand Basic Science of Tumor Development and Growth

The Cancer Biology program at the UAMS Winthrop P. Rockefeller Cancer Institute brings together investigators studying the basic biology of cancer at the molecular, cellular and in vivo levels. Program investigators use biochemical, genetic and other methodologies to study and understand the mechanisms of malignant transformation, tumor progression and tumor metastasis.

Steven Post, Ph.D., professor in the UAMS College of Medicine Department of Pathology, serves as program leader.

“Cancer biology is very broad based as it applies to basic science discovery. However, our program focuses on understanding the basic science as it relates to tumor cell development and how a cell’s environment either supports or inhibits tumor growth,” Post said.

These types of basic science discoveries are the building blocks that scientists in other areas need to conduct their own research.

“If a basic scientist identifies a process that inhibits tumor cell growth, researchers in therapeutics, for example, could design molecules that target that process, making it more difficult for tumors to grow or spread. This could lead to clinical trials of new therapies, bringing clinical relevance to our initial laboratory discovery,” Post said.

Program members are focused in three main areas:

Viral oncology, which includes both how viruses initiate tumor formation and how viruses can be used to target tumor cells
Tumor immune response, which looks at how T cells change their behavior in a tumor and how those changes can be reverted back to the normal immune response
Vaccine targets, which examines new targets for vaccines and how to make them more effective

Since Cancer Biology was named one of the Cancer Institute’s four research programs in late January 2020, Post and his fellow members continue to solidify the program’s short- and long-term focus. A major goal includes encouraging program members to publish research and submit grants together, as well as collaborate with members of other research programs in the Cancer Institute.

“We need to have interactions across program lines where we establish co-authorships and collaborations between programs,” Post said.

After spending his early career researching cardiovascular health, Post moved into the cancer arena after discovering that the protein he studied also played a fundamental role in the microenvironment of tumors. Similarly, he said, researchers focused on other disease sites may also find unexpected connections to cancer research.

“There is a lot of overlap in biomedical research that allows people to transition their focus from other areas to cancer and bring new ideas to the table,” Post said.