Development of Anticancer Peptides


Dr Mingliang He,
Associate Professor,
Department of Biomedical Sciences (BTC)


Cancer is the second killer of human diseases worldwide. It is reported that there are 14 million new cancer cases every year. By estimation, the new cancer cases would increase to 22 million in year 2035 and cancer-related deaths would also increase from 8.2 million to 13 million accordingly. In China, the newly diagnosed cancer cases are about 3.4 million with 2.1 million deaths annually, account for 25% all deaths of cancer worldwide.

Peptide/protein drug is undoubtedly new market in the near future because it offers great advantages over small molecules, including high biological activity, high specificity and low toxicity [1]. This represents an important direction for drug development. For the period 2009-2011, only 34 (45%) small molecules were approved by FDA, while 18 (24%) peptides (or proteins) were introduced into market. Considerating that far fewer academic and industrial investment in peptide drug development, obviously, peptides are much more successful as therapeutics than small molecules. The value of peptides is about 14.1 billion US dollars in 2011 and will be 17 billion in 2018, and constantly increases by 20~25% annually.

Many factors, including chemical and environmental carcinogens, virus infections (such as HBV/HCV infection), dysfunction of tumor suppressor genes, and amplification or false activation of proto-oncogenes, contribute to the carcinogenesis and the process of tumor development. TBX2 and TBX3 are highly conserved oncogenes which are amplified in and contribute to multiple cancer development, including breast cancer, liver cancer, bladder cancer, melanomas, ovarian cancer, and colorectal cancer. The conserved transcriptional repressor domain of TBX2/TBX3 is essential to the tumor growth.

We have developed an anticancer peptide TAP21 (Chinese Patent No. 201010110980.2), which can specifically antagonize oncoprotein TBX2 and TBX3. In the past years, we have done a lot of work oncoprotein TBX2 and TBX3. Supported by RGC-GRF, we figured out that 10 residues are crucial for TBX2/TBX3 functions. With the support of ITF (Tier 3, ITS/080/08), we developed an antagonizing TBX2/TBX3 peptide TAP21, which shows potent anticancer activities both in vitro and in vivo.

TAP21 can specifically inhibit growth of cancer cells by induction of cell cycle arrest and apoptosis without detectable effects or toxicity on normal cells. Further supported by The Science Technology and Innovation Committee of Shenzhen Municipality (重点攻关:JSGG20151030110921727), we have shortened the peptide from 81 residues (including tags) to 20-25 residues. Now we are design the new version anticancer peptide to extend its half-life and to further enhance its bioactivities by chemical modification for clinical applications.