Taiwan: A
research team led by Dr. Han-Chung Wu, a Research Fellow at the
Institute of Cellular and Organismic Biology, Academia Sinica has
successfully identified three novel peptides with high specificity and
binding affinity to colorectal cancer cells that could vastly improve
the efficacy of anti-cancer chemotherapeutic drug delivery systems. The
research team used the peptides to develop a novel targeted liposomal
drug, which showed marked cancer cell growth inhibition without any
adverse effects in animal models. These significant discoveries were
published in the journal Science Translational Medicine on June 3, 2015.
Colorectal cancer is one of the most
commonly diagnosed cancers and a leading cause of cancer death
worldwide. Traditional chemotherapy only has limited therapeutic
efficacy due to non-specific delivery to tumor and non-tumor cells, and
the development of drug resistance by cancer cells. Therefore, there is
an urgent need to develop more tumor-specific targeted drug delivery
systems that can more accurately and effectively deliver the anti-cancer
chemotherapeutic drugs to the tumor sites.
In the study, Mr. Chien-Hsun Wu, the
first author of the article, used phage display technology to identify
three peptides that could bind to colorectal cancer cells with high
specificity and binding affinity. Mr. Wu also found that these peptides
could bind cancer cells obtained from the biopsy of colorectal cancer
patients.
The research team then successfully
concocted a targeted drug by conjugating these peptides to liposomes.
This novel targeted liposomal drug combination could accurately deliver
chemotherapeutics to tumors, resulting in a much higher dose of drugs
being accumulated at the tumor site. This significantly increased the
tumor inhibition abilities of these two types of chemotherapeutic drugs
and effectively eliminated cancer without inducing any side effects for
150 days, with no trace of recurrence.
Professor Han-Chung Wu, the Principal
Investigator of the group, said that small molecule drugs have the
advantage of having higher tumor penetration abilities, but they are
non-specific to tumors and have short half-life. The protein drugs are
highly tumor-specific; however, they have lower tumor penetration
abilities due to their large molecular sizes. The research team designed
an effective targeted drug delivery system through an innovative
approach by combining the potent small molecule drugs with highly
specific protein targets, thus leveraging the benefits of the two
therapeutic regimens while reducing their disadvantages. The efforts of
the research team have led to the development of a new cancer treatment
that increases the therapeutic efficacies of the drugs while reducing
their side effects, thereby effectively curing cancer.
“Although there have been continuous
discoveries of new cancer drugs,” said Dr. Ruey-Long Hong; “most of the
drugs have only limited efficacy against cancer with less than ideal
effects on prolonging the lives of cancer patients. The research team
ingeniously overcame the challenge of accurately delivering the drugs to
the tumor sites by combining the liposomal drugs with peptides
generated using phage display technology to design a new generation of
targeted anti-cancer drug delivery system. The results from this study
will provide significant contributions to cancer treatment.”
In addition to successfully designing a
targeted drug delivery system against colorectal cancers, the group has
also developed targeted drug delivery systems against lung, liver and
breast cancers. In the future, these research results are expected to
dramatically improve the quality of lives for cancer patients when
applied to cancer therapy and early diagnosis.
The affiliations of the research team
were Dr. Han Chung Wu, Research Fellow at the Institute of Cellular and
Organismic Biology, Academia Sinica; Chien-Hsun Wu, a PhD candidate at
the Graduate Institute of Life Sciences (a graduate school co-sponsored
by National Defense Medical Center and Academia Sinica); Yi-Huei Kuo, a
research assistant; and Dr. Ruey-Long Hong, an oncologist at the
National Taiwan University Hospital.
The complete article entitled
“α-Enolase–Binding Peptide Enhances Drug Delivery Efficiency and
Therapeutic Efficacy Against Colorectal Cancer” can be found at the
Science Translational Medicine journal website at: http://stm.sciencemag.org/content/7/290/290ra91.short?rss=1