National Cancer Research Month: therapies to watch

By Bruce Lieberman
May 30, 2013

As National Cancer Research Month draws to a close, we profile important work by three Sanford-Burnham researchers in this last post of our May cancer research series: Drs. Erkki Ruoslahti, Maurizio Pellecchia and Ranjan J. Perera.

Developing smarter cancer drugs

The conventional battle against cancer can lay waste to the body. Chemotherapy drugs and radiation therapy are intended to kill cancer cells, but their side effects are akin to collateral damage in a war – and they can be devastating.

But what if cancer drugs could be targeted only to the tumors where they’re needed, while sparing healthy tissues?

Erkki Ruoslahti, M.D., Ph.D., and colleagues have developed a short-protein molecule, or peptide, called iRGD that homes in on cancer tumors. Cancer drugs attached to this peptide can penetrate deeply into tumors. Experiments in mice have shown that these combination “smart drugs” are effective in treatments against human breast, prostate, and pancreatic cancers. And, because the combination therapy is targeted specifically to where it’s needed, two thirds less of the cancer drug is needed to achieve the same effect.

Dr. Ruoslahti and his team believe their work may transform the way physicians treat cancer. Because the iRGD peptide can be co-administered with cancer drugs, there is no need to modify existing drugs. That means existing treatments can be mixed with the peptide and tested right away. The iRGD technology has been licensed to the biotechnology company CendR Therapeutics, Inc., which is now working with collaborators at a major hospital to begin testing peptide treatments in humans.

Inducing cell death in tumors

Tissues in the body are constantly renewing themselves, and as new cells form others must die. This natural process of cell self-destruction, called apoptosis, is a normal phenomenon that can go haywire in cancer.

Work by Maurizio Pellecchia, Ph.D., has contributed to the discovery of a process related to apoptosis that is now leading to the development of new cancer drugs. Dr. Pellecchia and colleagues found that one or more of a family of proteins called Bcl-2, which helps cells avoid apoptosis, are overproduced in most human cancers. This overexpression makes cells resistant to many cancer treatments.

Sanford-Burnham has used this knowledge to partner with a biotechnology company called Oncothyreon, Inc. to develop a novel drug called sabutoclax. Sabutoclax inhibits the Bcl-2 family of proteins, and by blocking their function the drug induces apoptosis in tumor cells. That, in turn, makes chemotherapy drugs more effective.

Taking another look at “junk RNA” in melanoma

RNA, or ribonucleic acid, is a ubiquitous molecule that plays a fundamental role in the expression of genes and the generation of proteins within cells. But until about a decade ago, it was thought that only about three percent of RNA molecules actually had an active role. The rest of them were “junk”; in other words, they didn’t have any function.

Now, researchers know that a lot of non-coding RNA, informally referred to as “junk RNA,” in fact switch genes on and off and perform a wide variety of functions seen in embryonic development as well as in diseases, including cancer.

Ranjan J. Perera, Ph.D., and colleagues at Sanford-Burnham’s Lake Nona campus have found that some non-coding RNAs are involved in the development of a type of skin cancer called melanoma as well as in prostate cancer. Levels of one type of non-coding RNA molecule, called SPRY4-IT1, are elevated in melanoma and prostate cancer, while levels of another type, called miR-211, are depressed. These discoveries may allow physicians to identify the development of these cancers earlier, through blood tests rather than biopsies.

In other work, Dr. Perera and his colleagues have found that a process called methylation, in which small molecules are linked to DNA and therefore alter the expression of genes, is heightened in stage 2, 3 and 4 melanoma cells.

Methylation, which adds a methyl group to DNA and therefore modifies gene expression, is one of many changes to DNA that can occur in a process called epigenetics. Because each person’s epigenetic markers are unique, knowing the epigenetic signature of a patient’s cancer can allow doctors to tailor treatments for that person. Continued studies could lead to a type of personalized medicine to treat melanoma and other cancers, says Dr. Perera.

National Cancer Research Month is not over until Friday, so keep following the conversation on Twitter, #NCRM13.

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