Kate Zaytseva, one of four project leaders on the COBRE grant for the Center for Cancer and Metabolism, and postdoc Naser Jafari are studying the importance of an enzyme called fatty acid synthase in controlling survival and spread of colorectal cancer.

UK wins $11.2 million NIH grant to study cancer-obesity link

UK has been awarded an $11.2 million grant from the National Institutes of Health to study the link between cancer and metabolic disorders, including obesity. The prestigious award will enable UK to launch the UK Center for Cancer and Metabolism (CCM).

The Centers of Biomedical Research Excellence (COBRE) grant to study the metabolism of cancer comes from the NIH’s National Institutes of General Medical Sciences and will fund the UK Center for Cancer and Metabolism over the next five years.

Kentucky has disproportionately high incidences of both cancer and metabolic disorders – our state leads the nation in cancer deaths and is in the top 10 for highest obesity rates in the country. While scientists have long known of a direct link between obesity and cancer, the need for further research into this field is a necessity for Kentuckians.

Senate Majority Leader Mitch McConnell of Kentucky, an advocate of the 21st Century Cures Act, contacted NIH Director Francis S. Collins on behalf of UK’s grant application.

“In an effort to improve healthcare access and outcomes for my constituents, UK has long made a priority of undertaking important research specific to Kentucky and the Appalachian region,” McConnell said.

“Over the years, UK and its Markey Cancer Center have developed one of the strongest cancer research, prevention and treatment programs in the country, as demonstrated by the center’s 2013 NIH National Cancer Institute designation, which I was proud to support. I was also pleased to assist UK in securing this competitive grant to advance and strengthen this critical health research for Kentucky by enabling advanced research focusing on the development of novel therapies for cancer treatment.”

Kentucky Representative Andy Barr echoed McConnell’s sentiments, noting that support and funding for innovative cancer research remains a priority.

“The awarding of this competitive grant is a recognition of the University of Kentucky as a national leader in biomedical research,” Barr said. “I have consistently supported the National Institutes of Health because these investments not only contribute to our local communities and institutions, they will improve and even save lives by advancing new treatments and cures. I am confident the healthcare services provided by the NCI-designated Markey Cancer Center and the research done by UK scientists funded by this grant will help us to find better ways to fight cancer, which will benefit patients and families in Kentucky and around the world.”

Linking metabolism and cancer

The UK Center for Cancer and Metabolism capitalizes on highly specialized institutional strengths in cancer and advanced metabolomics tools to focus on the underlying mechanisms that link dysfunctional metabolism to cancer. Recent studies have shown that the metabolic powerhouse of cells – the mitochondria – can influence how aggressive a cancer becomes.

UK has internationally renowned experts in the field of cancer and metabolism, and new state-of-the-art technology has improved the ability to understand how metabolism impacts cancer.

“As the University for Kentucky, we are uniquely positioned to conduct this level of sophisticated research thanks to the presence of a diverse array of biomedical researchers, clinicians and our leading academic medical center,” UK President Eli Capilouto said. “Research and development is at the core of economic and human development, and it is why UK is Kentucky’s most instrumental change agent, health provider and economic engine. The progress we make offers the brightest future and best hope for Kentucky.”

The CCM will bring together highly complementary disciplinary strengths at UK in cancer, metabolism and data sciences, coupled with sophisticated metabolomics tools and advanced cancer imaging capabilities, to strengthen the university’s cancer research enterprise by providing a thematically focused multidisciplinary infrastructure dedicated to defining the role of metabolism in the development and treatment of cancer.

“Research is at the heart of any progress we hope to make in bridging health gaps in the Commonwealth,” said Lisa Cassis, UK vice president for research. “Increased funding opportunities through the 21st Century Cures Act, and in particular this COBRE focused on cancer and metabolism, will enable the university to foster the development of the next generation of scientists who will lead our efforts in translating basic research findings into promising new therapies.”

Fighting back against cancer in Kentucky

The scientific discoveries achieved through the CCM will continue to help the UK Markey Cancer Center in its mission to conquer cancer in the Commonwealth. As Markey prepares to renew its National Cancer Institute Cancer Center designation, and simultaneously compete to become a Comprehensive Cancer Center later in 2017, Markey Director Dr. Mark Evers emphasizes the need for increased cancer research funding and continuing to push for new discoveries.

“Nowhere in the country is it more important to have this level of cancer research underway,” Evers said. “Kentuckians face a unique set of health issues, but we at the UK Markey Cancer Center are distinctly positioned to help solve the problem. Being an NCI-designated cancer center means being a leader in research as well as clinical care and outreach. This funding will allow us to translate our findings into potential new therapies for cancer patients from Kentucky and beyond.”

The CCM leverages expertise with mentors and collaborators from across multiple UK centers, disciplines and departments. The multidisciplinary collaboration is indicative of the type of work ongoing at UK and UK HealthCare every day.

“This new funding is another example of the vital importance to the people of Kentucky – and this region – in having an academic medical center at the University of Kentucky,” said Dr. Michael Karpf, UK executive vice president for health affairs. “The synergy and collaboration between researchers and clinicians to further studies in cancer can only be done at a place like this, where people are working together to make a difference in the lives of patients now and for generations to come.”

Promoting collaboration

COBRE grants also use this platform to develop promising early-stage investigators with enhanced skillsets in exciting new areas of cancer research and to enhance their success in competing for NIH grant support. The grant promotes collaborative, interactive efforts among researchers with complementary backgrounds, skills and expertise.

Four junior investigators, mentored by teams of clinicians and scientists from a variety of disciplines, departments, and colleges at UK, will lead major projects investigating an aspect of cancer metabolism:

  • “Role of vitamin D in protecting against cachexia in cancer patients,” led by Travis Thomas, Department of Clinical Sciences, UK College of Health Sciences
  • “Role of serine biosynthesis pathway in breast cancer,” led by Yadi Wu, Department of Pharmacology and Nutritional Sciences, UK College of Medicine
  • “Role of RORα in breast cancer metastasis,” led by Ren Xu, Department of Pharmacology and Nutritional Sciences, UK College of Medicine
  • “Role of fatty acid synthase in colorectal cancer,” led by Kate Zaytseva, Department of Toxicology and Cancer Biology, UK College of Medicine

The CCM is co-led by program directors Daret St. Clair, professor and James Graham Brown Foundation Endowed Chair in the UK Department of Toxicology and Cancer Biology, and Peter Zhou, professor in the UK Department of Molecular and Cellular Biochemistry.

“Having the kind of environment where learning and collaboration are placed at the forefront is why we were chosen for this grant, and we hope to continue that throughout the life of this center,” St. Clair said. “It will also enable us to reach out to new and talented researchers who want to come to UK to become new project leaders and continue the work we’re doing.”


Watch the video below to learn more about the Center for Cancer and Metabolism.


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A new study, done in part at the UK Markey Cancer Center, shed light on why lung cancer cells can resist therapeutic cancer treatment.

Markey research sheds light on lung cancer formation and treatment

A new study co-authored by a researcher starting her laboratory at the UK Markey Cancer Center shows that in certain genetic situations, one non-small cell lung cancer subtype can change into another subtype.

This lung cancer “lineage switching” could explain why some cancers are resistant to therapeutics, and this research examines exactly how the lineage switch can happen. The work was a collaborative effort between laboratories in Kentucky, New York and Boston.

“Now that we have a glimpse into the molecular mechanism of lineage switching, we can begin to learn how to manipulate this phenomenon for better therapeutic outcomes,” said study co-author Christine Fillmore Brainson, assistant professor in the UK Toxicology and Cancer Biology department.

Previously, it was unclear which cells in the adult lung can be the “cells-of-origin” of the two major subtypes of non-small cell lung cancer, namely adenocarcinoma and squamous cell carcinoma. Likewise, it was unclear what differences in DNA organization define the two distinct lung cancer subtypes. The existence of adenosquamous lung tumors, clinically defined by the presence of both glandular adenocarcinoma lesions and fully stratified squamous lesions within the same tumor, suggested that both adenocarcinomas and squamous cell carcinomas could come from the same cells in the lung, but clear evidence for this theory was lacking.

Published in Nature Communications, the study showed that adenocarcinoma cells can change to squamous cells due to reorganization of their DNA in specific ways. Beginning with a mouse model of adenosquamous lung tumors, researchers validated the genetics by comparing it to human adenosquamous lung tumor – the genetics are often the same, including activation of the oncogene KRAS and the deletion of the tumor suppressor Lkb1. The team then used transplant assays to demonstrate that established adenocarcinoma tumors could transition to squamous cell carcinomas in the mouse lung.

Lastly, the group isolated different lung cells, and demonstrated that only certain lung cells could give rise to tumors capable of undergoing the lineage switch.

“This data is exciting because it shows which cells in the lung can give rise to adenosquamous tumors,” Brainson said.  “And the technique we used to transform the isolated cells can be applied to many lung cancer models.”

Oncologists have observed this “lineage switching” after the failure of EGFR tyrosine kinase inhibitor treatment, when it is clinically justifiable to take a second biopsy. However, second biopsies are not normally done after chemotherapy, a practice that Brainson thinks could be revised to understand the exact mechanisms of therapy resistance.

In addition to Brainson, the manuscript was co-authored by Haikuo Zhang of the Dana-Farber Cancer Institute in Boston. The research was a collaborative effort between the laboratories of Carla Kim at Boston Children’s Hospital, where Brainson was based for her post-doctoral studies; Hideo Watanabe at Icahn School of Medicine in New York; and Dr. Kwok-Kin Wong at Pearlmutter Cancer Center in New York.

This work was funded in part by the American Cancer Society, the Lung Cancer Research Foundation, the V Foundation for Cancer Research, the March of Dimes, the National Cancer Institute, the Gross-Loh Family Fund for Lung Cancer Research and Susan Spooner Family Lung Cancer Research Fund at the Dana-Farber Cancer Institute


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Kentucky’s death rate from cervical cancer ranks among the top 10 in the nation. But many of these deaths are preventable by regular Pap smears.

Pap smears: Your best weapon against cervical cancer

It’s an unfortunate fact that Kentucky has one of the highest cervical cancer death rates in the country. The good news is many of these deaths are preventable through regular screenings called Pap smears.

Pap smears collect cells from the cervix, which are examined under a microscope to find cancer and pre-cancer. If pre-cancer is found, it can be more easily treated, stopping cervical cancer before it really starts.

There are no obvious symptoms of cervical cancer until it reaches advanced stages, so having regular Pap smears is important. Federal guidelines recommend women ages 21 (or three years after first intercourse) to 65 have a Pap smear every three years during their annual pelvic exam. Individual circumstances can vary, so talk to your doctor about how often you should have a Pap smear.

Ways to improve test results

According to the American Cancer Society, there are several ways to make your Pap smear results more accurate:

  • Try not to schedule an appointment for a time during your menstrual period. The best time is at least five days after your menstrual period stops.
  • Don’t use tampons, birth-control foams or jellies, other vaginal creams, moisturizers or lubricants, or vaginal medicines for two to three days before the Pap test.
  • Don’t douche for two to three days before the Pap test.
  • Don’t have vaginal sex for two days before the Pap test.

Check with your doctor

Because Pap smears are often done during pelvic exams, many people confuse the two. The pelvic exam is part of a woman’s routine checkup that may help find other types of cancers and reproductive problems. During a pelvic exam, the doctor examines the reproductive organs, including the uterus and the ovaries, and may do tests for sexually transmitted disease.

Be sure to check with your doctor to see if you had a Pap smear during your pelvic exam.


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Dr. van Nagell has worked with countless patients, faculty and students, but his legacy will likely be Markey's Ovarian Cancer Screening Program.

Listen: Dr. van Nagell talks about his life-saving work at Markey

In 1987, Dr. John van Nagell started the UK Markey Cancer Center’s Ovarian Cancer Screening Program, an ongoing research endeavor that provides free ovarian cancer screenings by transvaginal ultrasound to women across Kentucky.

Now in its 30th year, the program has provided free screenings to more than 46,000 women and found 775 ovarian tumors and 103 malignancies. Screenings are provided to women over the age of 50 and to those over the age of 25 who have a family history of ovarian cancer.

Van Nagell was recently honored for his years of clinical, research and educational work on a national level, earning the Society of Gynecologic Oncology’s Distinguished Service Award for 2017.

We sat down with Dr. van Nagell to discuss his reaction to the award and what keeps him motivated in his fight against ovarian cancer in Kentucky. Listen to the conversation below.


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Despite being largely preventable, colorectal cancer is the third most common in the U.S., and Kentucky ranks first in the nation for incidence.

Most colorectal cancer is preventable; here’s what you need to know

Dr. Jitesh Patel

Written by Dr. Jitesh Patel, colorectal surgeon at the UK Markey Cancer Center.

Colorectal cancer is the third most common cancer in the U.S. In Kentucky, the disease is particularly bad: Our state ranks first in the nation for colorectal cancer incidence and seventh in deaths. More than 2,500 new cases of the disease are diagnosed each year in Kentucky, and colorectal cancer takes the lives of more than 800 Kentuckians annually. The good news is colorectal cancer is a largely preventable disease.

Cause of colorectal cancer

The disease originates when healthy cells from the innermost layer of the colon or rectum change and grow uncontrollably, forming abnormal tissue growths called polyps. These growths are usually benign, but they can eventually become cancerous if they aren’t removed in time.

Risk factors and symptoms

Age, genetics and lifestyle are all possible risk factors for colorectal cancer. The disease typically affects men and women age 50 and older, and people are more likely to have the disease if others in their family have had it. Additional risk factors include obesity, lack of exercise, smoking, high alcohol use, and a diet high in red or processed meat and low in calcium, fruits and vegetables.

Colorectal cancer signs are often ignored because the disease may start with few or no noticeable symptoms. Some observable symptoms include:

  • Change in bowel habits.
  • Recurrent abdominal pain or discomfort.
  • Rectal bleeding.
  • Weakness or fatigue.
  • Unintentional weight loss.

How it can be prevented

Regular screening tests, including colonoscopies, are recommended for everyone starting at the age of 50 as well as for people at a younger age who are at high risk of developing the disease. African-Americans should be screened starting at age 45. Colonoscopies can actually prevent colorectal cancer by finding the precancerous lesions/polyps, allowing your doctor to remove them before they become malignant and cause serious harm.

In addition to screenings, changing some of your lifestyle habits can help you lower your risk of colorectal cancer. Proactive lifestyle changes include exercising regularly, opting for a diet rich in vitamins and calcium, quitting smoking, and lowering alcohol consumption.

Treating colorectal cancer

Treatment depends on the stage of the cancer. Surgery to remove the cancer is usually the first and only required treatment in early stages. However, in more advanced stages, when the disease has spread into nearby tissue and organs, chemotherapy before and/or after the surgery and targeted therapy drugs may also be necessary.

Colorectal cancer is about 90-percent treatable when discovered in its earliest stages. While a colonoscopy may not be a fun experience, it could very well save your life.


Next steps:

  • Learn more about Markey’s gastrointestinal cancer team, which provides comprehensive, personalized care for cancers including colorectal cancer.
  • With other life events keeping her busy, Claudia Hall almost skipped a routine screening for colorectal cancer. She decided to keep the appointment, and it’s a decision that saved her life. Read Claudia’s story.
In 1987, Dr. John van Nagell began the Ovarian Cancer Screening Program. Now in its 30th year, the program is as successful and strong as ever.

Markey’s Dr. John van Nagell celebrates 30 years leading the Ovarian Cancer Screening Program

As a native Kentuckian, Dr. John van Nagell has always appreciated the impact UK has in the Commonwealth.

Van Nagell earned his undergraduate degree at Harvard University and his medical degree from the University of Pennsylvania, but his goal was to return to Kentucky to practice medicine.

“I always wanted to come home,” van Nagell said. “And when it came time for me to decide where I wanted to undergo further training, the University of Kentucky had just opened an outstanding new medical center.”

Specializing in gynecologic oncology – the diagnosis, research and treatment of women’s cancers – van Nagell joined UK HealthCare as a resident in 1967, about 16 years before the creation of the UK Markey Cancer Center. He’s spent his career at UK treating patients and mentoring young doctors, but his lasting legacy will likely be his research.

In 1987, van Nagell started Markey’s Ovarian Cancer Screening Program, an ongoing research endeavor that provides free ovarian cancer screenings by transvaginal ultrasound to women across Kentucky.

‘Committed as ever’

Now in its 30th year, the program has provided free screenings to more than 46,000 women and found 775 ovarian tumors and 103 malignancies. Screenings are provided to women over the age of 50 and to those over the age of 25 who have a family history of ovarian cancer.

“We’ve been able to detect ovarian cancer at an earlier stage in many women, rather than just waiting for symptoms to occur,” van Nagell said. “The survival rate of women in our program who have ovarian cancer is roughly double that of women who didn’t get screened.”

Although the use of transvaginal ultrasound as a screening method has been controversial – with critics suggesting it may lead to unnecessary surgeries – van Nagell emphasizes that newer technologies such as molecular genetic testing will help doctors identify at-risk women who could most benefit from screening. The research program has also taught physicians more about finding malignancies, van Nagell said.

“We now know, because of this screening program, that certain ovarian cysts are always benign,” he said. “What we’re saying is more research needs to be done, and we’re doing it. And if we can provide free screening along the way to an at-risk population, that’s beneficial.”

With 50 years of experience at UK under his belt, van Nagell says he remains “as committed as ever,” still dedicated to perfecting the work he began three decades ago for his patients.

“All you have to do is go back into the clinic and see one case after another of ladies coming in with advanced ovarian cancers who had no early symptoms, and by the time their symptoms developed, their disease was incurable,” he said. “And the most fulfilling part is just seeing women who didn’t realize something was wrong but had a potentially fatal disease, which we were able to detect through screening, successfully treat, and now they’re fine.”

Dr. van Nagell honored by his peers

Regularly cited as one of the “Best Doctors in America,” van Nagell recently received another major accolade from his peers. Earlier this month, he attended the 2017 Annual Meeting on Women’s Cancer in Baltimore, where he was presented with the Society of Gynecologic Oncology’s Distinguished Service Award. This award recognizes individuals who, over an extended period of time, display a continuous outstanding meritorious service in the field of gynecologic oncology.

“To be honored by your peers is very special,” van Nagell said. “And I believe that – at least in some small way – this validates what we have tried to do here, and that is to improve the early detection of a very serious disease. To me, it’s all about the lives of people who have been changed for the better by the screening program.”


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Todd Svoboda

Former Wildcat teams up with Markey experts to beat rare bone cancer

Although he rarely played, Todd Svoboda was a universally adored member of the 1993 UK men’s basketball team that made it to the Final Four, and will forever be linked to the Big Blue Nation.

Years after he hung up his basketball sneakers, Todd’s bond with UK became even stronger when he was diagnosed with a rare form of bone cancer. With the same toughness and perseverance that helped him on the hardwood, and with the help of an expert team at the UK Markey Cancer Center, Todd faced his disease head on.

Read Todd’s story and watch our video to find out how Todd is doing today.


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Dr. Mark Evers

Video: Markey hosts inaugural Precision Medicine Symposium

The UK Markey Cancer Center on Wednesday hosted its inaugural Precision Medicine Symposium, aimed at teaching oncology healthcare providers how to implement precision medicine into their clinical practice.

Precision medicine in cancer treatment focuses on understanding genetic mutations and using those mutations to select the best therapy for patients. Precision medicine is one of the recommendations highlighted by the White House Cancer Moonshot’s Blue Ribbon Panel. Presentations at Wednesday’s symposium included discussions about oncogenomic testing, Markey’s new Molecular Tumor Board, clinical trials and more.

Attending the symposium were more than 190 providers, including oncologists, hematologists, pathologists, radiologists, oncology nurses, researchers, pharmacists, genetic counselors, and cancer center administrators and leaders representing more than 20 different medical centers and healthcare entities across the region.

Breakout sessions allowed providers to meet in smaller groups with presenters and ask questions about precision-medicine issues, such as payment and reimbursement for Molecular Tumor Board recommendations.

The symposium concluded with a keynote speech from Dr. Shridar Ganesan, chief of molecular oncology at the Rutgers Cancer Institute of New Jersey.

“This event is so important because we want to bring precision medicine to all patients with cancer in Kentucky,” said Jill Kolesar, PhD, co-director of the Markey’s Molecular Tumor Board. “We’re bringing together clinicians and scientists to bring initiatives from the Markey Cancer Center to the entire Commonwealth of Kentucky.”

Watch a video below for more highlights from this exciting event.


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To increase the number of preventive colorectal screenings, the UK Markey Cancer Center will follow a National Cancer Institute (NCI) initiative.

Markey joins national colorectal cancer screening initiative

The UK Markey Cancer Center is joining a National Cancer Institute (NCI) initiative aimed at improving colorectal cancer screening rates among men and women aged 50 and older from racially, ethnically and geographically diverse communities.

The national Screen to Save (S2S) Colorectal Cancer Outreach and Screening Initiative is led by the NCI’s Center to Reduce Cancer Health Disparities.

Colorectal cancer is the second-leading cause of cancer-related deaths in men and women combined. Kentucky’s mortality rate is among the highest in the country, and more than 800 people in the state die from the disease each year.

Markey’s Mindy Rogers, a community health educator, will collaborate with state and regional organizations and community stakeholders throughout Appalachian Kentucky to conduct the initiative’s culturally tailored education and outreach.

“Colorectal cancer is a screenable cancer. The earlier we can find the disease, the better the chances of survival,” Rogers said. “The intent of this initiative is to provide additional community and regional resources to aid our efforts to improve cancer screening rates and save lives. The S2S effort complements many of our existing colorectal cancer outreach programs conducted by colleagues at Markey and its affiliates, the Kentucky Cancer Program and our local health departments.”

S2S stems from research recommendations from the Cancer Moonshot Blue Ribbon Panel and will be supported by the Geographic Management of Cancer Health Disparities Program Region 1 North, led by Dr. Mark Dignan, the co-leader of Markey Cancer Prevention and Control.


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A new study led by the UK Markey Cancer researchers establishes a novel link between cell polarity and cancer-associated inflammation.

UK study reveals insights into cancer-associated inflammation

A new study led by UK Markey Cancer Center researchers and published in the Journal of Cell Science establishes a novel link between cell polarity and cancer-associated inflammation.

Reactive oxygen species (ROS) are reactive molecules and free radicals derived from molecular oxygen. ROS molecules are part of the immune system’s “killing response” against microbial invasion. Using a 3-D co-culture model of breast cancer cells and monocytes, Markey researchers Ren Xu and Linzhang Li found that disruption of cell polarity is accompanied by increased ROS production, leading to increased inflammation in these cells. The increased ROS production controls monocyte/macrophage infiltration by inducing the NF-kB pathway in mammary epithelial cells. Loss of cell polarity and inflammation are hallmarks of breast cancer development.

Cancer is like a wound that never heals, characterized by the disruption of normal tissue structure and inflammation. However, it is unclear whether and how the loss of tissue organization causes inflammation. Moving forward, figuring out ways to reduce ROS levels in mammary epithelial cells is a potential strategy to limit cancer-associated inflammation and prevent cancer development and progression.

This research was funded through the American Heart Association and the U.S. Department of Defense.


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