Head and neck, breast cancer research highlights AACR abstracts

Vinita Takiar’s lab in UC’s Department of Radiation Oncology studies how to improve radiation therapy for head and neck cancer patients.  

Julianna Korns, a doctoral student working in Takiar’s lab, and her colleagues study an enzyme called Plk1 that allows healthy cells to divide and function normally. When overexpressed in head and neck cancer cells, it causes the cells to divide abnormally and at a faster rate, leading to the accumulation of more cancer cells. 

Using data from The Cancer Genome Atlas database, the research team found Plk1 overexpression was correlated with worse survival outcomes in head and neck cancer patients. Studying cell lines in the lab, they found blocking Plk1 reduces head and neck cancer cell growth. 

Interestingly, Korns noted that Plk1 inhibition reduces cell growth in head and neck cancer cells that are positive and negative for HPV, but HPV-negative cells are more sensitive to this treatment than HPV-positive cells. 

“Typically, HPV-negative head and neck cancer patients are more resistant to therapy, so this novel finding could provide benefit to HPV-negative head and neck cancer patients in the clinic,” Korns said. “Our study indicates a potential marker for treatment outcomes. Understanding the role of Plk1 is pivotal to optimizing treatment regimens for these patients.” 

Susan Waltz, PhD, studies the role of a gene that helps accelerate cancer growth called Ron in her laboratory in UC’s Department of Cancer Biology. Zhixin Lu, a doctoral student in Waltz’s lab, wanted to learn more about how Ron affects head and neck cancers while on a rotation in Takiar’s lab.  

Lu’s research bridges a collaboration between the Takiar and Waltz laboratories and between UC departments.  

“We have heavily studied this Ron receptor in breast cancer and prostate cancer, how it drives cancer metastasis and drug resistance,” Lu said. “Ron is heavily expressed in a lot of cancers, including head and neck cancer, but we know much less about its role in head and neck cancer. So that’s really the premise of my project.” 

Lu’s research found that Ron is overexpressed at high levels in multiple cell lines of head and neck cancer, which she said indicates it may play a role in the cancer cells’ function and growth. 

“Ron expression is correlated with worse patient survival outcomes and radiation resistance. The higher Ron is expressed, the less the patient is going to survive in terms of overall survival, which indicates it potentially has a very negative role in those patients,” Lu said. “This makes it a very promising target to study.” 

A protein called EGFR is also overexpressed in a majority of head and neck cancers, but anti-EGFR treatments have not been very effective to this point due to the cancers developing drug resistance. Interestingly, the researchers found there is an inverse correlation between Ron and EGFR expression in head and neck cancer cell lines and patient data. 

Future studies will aim to learn more about how EGFR and Ron interact and whether blocking Ron will make EGFR-targeted treatments more effective. Lu said the team is also looking to see if there is a similar inverse correlation between Ron and EGFR in breast cancer, which could provide more information on their interaction. 

As researchers learn more, Lu said Ron inhibitors could potentially become a more common treatment option for head and neck cancer patients. Current treatments still rely heavily on chemotherapy and radiation, which come with toxicity and side effects, but a small molecule target like Ron could reduce the dose of chemotherapy needed, she said. 

“It’s more precise because the small molecule really targets proteins and the oncogenic pathway, and combined with that, may not only reduce the side effect but also be more precise to the specific target,” Lu said. 

RON receptor tyrosine kinase in head and neck cancer: a potential target for overcoming resistance to anti-EGFR therapy will be presented by Lu April 16 from 1:30-5 p.m. during the Drug Resistance in Molecular Targeted Therapies 1 poster session. Co-authors on the project include Mathieu Sertorio, Takiar and Waltz.  

Read about community outreach and engagement research being presented at AACR.

Other abstracts being presented by Cancer Center researchers include:

• FOXA2 induces invasive mucinous adenocarcinoma of the lung in the presence of mutant KRAS, presented by Yutaka Maeda April 17 from 9 a.m.-12:30 p.m. during the Gene Regulation in Solid Tumors poster session.
• Pan-cancer splicing analysis reveals shared drivers of malignant transformation and survival, presented by Anukana Bhattacharjee April 17 from 1:30-5 p.m. during the Bioinformatics Applications in Cancer Biology 2 poster session.
• Role of her3 v104l mutation on tumor growth and her3 stabilization, presented by Rosalin Mishra April 18 from 9 a.m.-12:30 p.m. during the Identification of Molecular Targets 1 poster session.
• RON receptor signaling enhances prostate cancer metastasis in Hi-Myc mice, presented by Angelle D. Jones April 17 from 9 a.m.-12:30 p.m during the EMT and Plasticity poster session.
• Identification of resistance mechanisms to direct KRAS inhibition in pancreatic cancer, presented by Andrew Waters April 16 from 1:30-5 p.m. during the Precision Molecular Subtyping and Therapeutic Development poster session.
• The role of HER3 mutations in the progression of colon cancer and modulation of drug sensitivity and resistance, presented by Mary K. Kilroy April 18 from 9 a.m.-12:30 p.m. during the Oncogenes and Tumor Suppressor Genes as Targets for Therapy 3 poster session.