Will this tumor cause trouble? Need treatment? Researcher seeks answers in gene he discovered

Still images from two videos of prostate cell growth. The cluster of cells on the top, in blue, are spherical, indicating healthy cell growth. The images on the bottom, which has had the gene/protein Abi1 removed, show cell clusters that are nonspherical and loosely attached, and are trying to migrate out. (FROM THE LAB OF LESZEK KOTULA, MD, PhD)

Still images from two videos of prostate cell growth. The cluster of cells on the top, in blue, are spherical, indicating healthy cell growth. The images on the bottom, which has had the gene/protein Abi1 removed, show cell clusters that are nonspherical and loosely attached, and are trying to migrate out. (FROM THE LAB OF LESZEK KOTULA, MD, PhD)

BY AMBER SMITH

Ever since he discovered a gene that causes prostate cancer 20 years ago, Upstate cancer researcher Leszek Kotula, MD, PhD, has focused on understanding the mysteries of the cancer that, besides skin cancer, is most common in men.

Leszek Kotula, MD, PhD (PHOTO BY WILLIAM MUELLER)

Leszek Kotula, MD, PhD (PHOTO BY WILLIAM MUELLER)

Much of his career is devoted to prostate cancer – because of the numbers.

Each year, 23 million men undergo prostate-specific antigen screening tests. Some 1.2 million men who are found to have high PSA levels undergo a biopsy. Some 240,000 are diagnosed with prostate cancer.

The vast majority of those men will have tumors that are noninvasive. About 3 percent will have an aggressive form of the disease that is difficult to treat.

That 3 percent represents some 7,200 husbands, fathers, brothers.

Those are the numbers that concern Kotula.

He dreams of being able to tell men who are diagnosed with prostate cancer more definitive news about their future. He wants to answer whether they have a tumor that will lie quietly within their prostate and cause no trouble, or a tumor that will spread to other organs and require treatment.

Kotula wants to be able to predict which tumor will remain indolent, and which will become invasive.

If he can do that, he can save lives.

Working together, Kotula’s team of biochemists and cell biologists uses a genetic engineering technique to study the disruption of “Abi1,” the gene he discovered in 1998.

They want to learn how the gene interacts with other genes and whether it plays a role in leukemias, breast, ovarian and other cancers.

Disharee Das, left, a doctoral student in biochemistry and molecular biology, puts a cell sample into a liquid nitrogen tank with help from her mentor, Kotula. (PHOTO BY WILLIAM MUELLER)

Disharee Das, left, a doctoral student in biochemistry and molecular biology, puts a cell sample into a liquid nitrogen tank with help from her mentor, Kotula. (PHOTO BY WILLIAM MUELLER)

“If we are successful, then we can make an impact on treatment,” Kotula says.

Discovering the Abi1 gene set him on this course.  Fast-forward two decades, and Kotula is focused on the function of the Abi1 gene. Its presence seems to inhibit prostate cancer, while the loss of function of this gene leads to prostate cancer.

Today his research involves three cell lines, one purchased commercially, one from genetically engineered mice at Upstate, and one from Upstate’s biospecimen bank, where some patients donate tissue from their tumors.

Looking under the microscope before the Kotula gene is removed – the scientific term is “”gene knockout” — the cells look as if they were melting into one big blob, and that blob spins.

The spinning stops when the gene is removed, and the cells are more individual, like a cluster of grapes. Some cells start to move out from the blob. “That’s where the process of invasion occurs,” Kotula says, explaining the moment the cancer begins to spread at the cellular level.

So far, there’s no easy way to tell when that occurs in an individual. Once cells metastasize to the lung or the bone, a patient’s tumors become visible through medical imaging. Before that happens, cellular changes aren’t visible.

But one day, Kotula hopes, doctors may be able to read a man’s genetics and tell him whether he has an aggressive form of cancer, or not.

About prostate cancer

When a man turns 60, his chance of developing prostate cancer soars. The American Cancer Society says three in five men over the age of 65 will develop prostate cancer.

It’s the most common cancer in men, other than skin cancer, and it is the third leading cause of cancer death in men, behind lung cancer and colorectal cancer.

The American Cancer Society projects that almost 27,000 men will die from prostate cancer this year.

Cancer Care magazine fall 2017 coverThis article appears in the fall 2017 issue of Cancer Care magazine.

 

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