Gregory Otterson, MD
Miguel Villalona, MD
and Christoph Plass, PhD 

Miguel Villalona, MD, left, Gregory Otterson, MD, right, and Christoph Plass, PhD (inset)

Lung cancer is the leading cause of cancer death among men and women worldwide, but patients can benefit from a multimodality, research-based approach to treating this genetically complex disease.

Among many scientists studying lung cancer at OSU are Gregory Otterson, MD, Miguel Villalona, MD, and Christoph Plass, PhD. All are members of the OSU Comprehensive Cancer Center and all played major roles in important studies in 2004.

One study found that a protein that can flag an important tumor-suppressor gene for destruction may be a key player in lung cancer development. Writing in the Journal of the National Cancer Institute, Villalona, Otterson, and lead author Wenrui Duan, PhD, note that the protein, called Pirh2, when overexpressed (too active), diminishes the p53 tumor-suppressor gene’s ability to regulate cell growth and death. This paves the way for the runaway cell growth that characterizes cancer.

“When p53 is not working properly, it can be disastrous,” says Villalona, senior author of the study, who notes that this is the first time Pirh2 has been implicated in the loss of p53 function in tumors.

“This is the first demonstration that Pirh2 expression is elevated in patients’ tumors, and it supports the notion that it may be an important molecule in lung cancer,” adds Otterson, co-author of the study. These findings may give scientists a new target for clinical intervention.

In another study, published in a 2004 edition of the journal Oncogene, Plass and Zunyan Dai, PhD, reported their discovery that aberrant methylation of a gene called BM P3B (bone morphogenic protein 3B) is often involved in non-small cell lung cancer (NSCLC), the most common form of the disease.

Methylation is a natural chemical process through which cells deregulate or “turn off” unneeded genes. Properly regulated methylation is important for normal biological development, but aberrant methylation contributes to cancer by silencing tumor-suppressor genes that would normally prevent improper cell division.

Plass says several other genes are frequently and improperly methylated in lung cancer, and all of them could be targets for therapeutic intervention.

He led an international study that in 2000 showed aberrant DNA methylation leads to cancer much more than previously thought. Plass is credited with discovering the non-random and tumor-type specific nature of promoter methylation in cancer.

Lab team collaborators for Drs. Otterson, Villalona and Plass include: Martin Brena, student; Zunyan Dai, PhD; Wenrui Duan, PhD; Li Gao, lab tech; Kavitha Kosuri, DO; Laura Smith, PhD; and Xin Wu, PhD.