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RASER proteins selectively “hack” and “shut down” cancer cells

According to World Health Organization, cancer is the second leading cause of death worldwide. The record showed that it caused about 9.6 million deaths last year (2018). Accordingly, one in every six deaths is attributed to cancer.[1]

Cancer defined

Cancer refers to the disease that arises from the faulty uncontrolled proliferation of cell, usually at a rate faster than the normal, and spread to other parts of the body. Benign tumors are also a form of atypical cell proliferation. However, the latter does not spread.

Pathophysiology in cancer cells

Why cancer cells lead to a disease is largely due to the tendency of the cancerous cell to detach and leave its original location to set itself to another site in the body. It could spread locally or drift through the bloodstream and lymphatic system to reach distant parts of the body. As a result, the affected body part eventually cannot carry out its function as it normally would due to the obstructing cancer cells that ought not to be there in the first place. Under those circumstances, our immune system is fashioned to detect cells that have gone “rogue” and then respond by eliminating them accordingly. Nevertheless, cancer cells tend to undergo series of mutations until such time that the genes for tumor suppression have been significantly inactivated while the proto-oncogenes modify into oncogenes.

RASER proteins

A novel approach dubbed as RASER (Rewiring of Aberrant Signaling to Effector Release) showed promising results when it killed cancer cells grown in the lab while sparing non-cancerous healthy cells. Researchers from Stanford Medicine[2] designed RASER system, which, in essence, consists of two proteins fused together. Accordingly, the first protein responds to cancer-causing cell surface signals. It does so by binding to active ErbB receptors, which are always “on” (expressed) in cancer cells. The second protein redirects the cancer cell from cell growth and survival toward programmed cell death (by releasing a customizable “cargo” into the cell). When the first protein binds to an active ErbB receptor, the second protein component is cut off from the RASER moiety and then binds to the inner surface of the plasma membrane of the targeted cell. The researchers customized the “cargo” sequence that the second protein carries. Once inside the cell, the second protein releases the RASER “cargo” — in this case, one that triggers the cell to undergo cell death.[2]


Top:  Illustration of cancer growth where cell surface proteins signal the nucleus to proliferate uncontrollably and survive (see green pathway). Bottom: Illustration of how RASER works by redirecting the signal away from cell proliferation and survival toward programmed cell death (see orange pathway). Image credit: Michael Lin and Stuart Jantzen (Ref.2)

One of the researchers, Michael Lin, MD, PhD, said that with this new approach they could rewire cancer cells and bring about an outcome according to their choosing. Furthermore, he said, “We’ve always searched for a way to kill cancer cells but not normal cells. Cancer cells arise from faulty signals that allow them to grow inappropriately, so we’ve hacked into cancer cells to redirect these faulty signals to something useful.” [2]

Although it could take time, still, the conception and the future progress of RASER is an auspicious cancer treatment. In due course, cancer patients may reap from its stance of being more highly selective to cancer cells while sparing the healthy ones in which the current cancer treatments are failing at.

— written by Maria Victoria Gonzaga

References:

1 World Health Organization (WHO). (2018, September 12). Cancer. Retrieved from Who.int website: [Link]

 2 Conger, K. (2019). Synthetic biology used to target cancer cells while sparing healthy tissue. Retrieved from News Center website: [Link]