Dr Abdullah Al-Hadi from University of Malaya (UM) was awarded RM30,000 by the National Cancer Council Malaysia (MAKNA) for his research in developing an oral anticancer drug that holds the potential to circumvent the limitations of other more invasive treatment methods.

“I want to make an alternative, less invasive treatment for colorectal cancer," said Dr Abdullah in his presentation during the MAKNA award ceremony.

When asked about his choice of colorectal cancer as the focus of his research, Dr Abdullah revealed that this type of cancer is among the most prevalent cancers in Malaysia. A local study published in Asian Journal of Surgery stated that colorectal cancer was the second most common cancer found in Malaysian males, and the third most common cancer in Malaysian females.(1) Estimates from available data suggested that out of every 100,000 Malaysians, around 21 of them will be diagnosed with colorectal cancer every year.(2) There is a significant ethnic influence as well, where people of Chinese ethnicity suffer a higher risk of developing this cancer compared to people of Malay, Indian or other ethnicities. (2,3)


The burden of colorectal cancer

Colorectal cancer can be treated via surgery, chemotherapy, radiotherapy or a combination of these treatments. Each treatment modality would present its unique challenges as well as different efficacy at eliminating these dangerous cancer cells. Advance treatments such as immunotherapy are emerging but none of these treatments is capable of completely curing the disease.

Furthermore, it can be difficult to improve treatment efficacy, as shown in the relatively high mortality rate of colorectal cancer. Studies showed Malaysia lacked behind neighbouring countries such as Singapore and Brunei in colorectal cancer survival rate. Data indicates that at any given year, the number of patients who die from colorectal cancer was approximately half of the number who were diagnosed in the same period of time, i.e. mortality-to-incident ratio was 0.51.(2)

Another issue that concerns Dr Abdullah is the nature of the currently available treatments. "If you look through all these four types of treatments, there is one thing in common, which is they are all very invasive and can be very harsh on the patients," he explained.

Hence, Dr Abdullah believes that there is an urgent need to explore alternative treatments that are safer, with higher precision at targeting cancer cells and less problematic to the patients.

He believes that his work will be pivotal in the search for such an alternative treatment.

A “homing device” that target cancer cells

His research idea revolves around the development of an oral anti-colorectal cancer drug that is highly selective towards the cancer cells by leveraging on specific "homing device" that can differentiate healthy and harmful cells. Colorectal cancer cells display specific markers on their surface, which, theoretically, could be exploited as targeting molecules.

After weeks of searching and screening through potential compounds, Dr Abdullah decided to focus on a peptide known as TCP-1. The compound is a vasculature-targeting peptide that displays promising tumour targeting ability. Previous animal studies, which were conducted independently from Dr Abdullah's laboratory, showed that the TCP-1 peptide had a significantly higher affinity, or homing ability, towards the vasculature of colorectal cancer tissues in mice (4,5).

Moreover, the peptide demonstrated a high level of specificity where it binds only to the tumours but not other tissues. Dr Abdullah believes that by the TCP-1 peptide can be stabilized for drug delivery by combining this peptide with the drug and a liposome, which helps with the digestion of the drug.

He also mentions that the homing ability of the TCP-1 peptide has been proven. A quick search through the literature will return years of cell-based and animal studies that investigated the unique properties of the TCP-1 peptide. However, it remains to be seen whether these preclinical studies will translate into disease treatment and effective use in clinical practice. There is more work to be done on that road ahead, and with the grant, Dr Abdullah is ready to take on the challenge of making that journey. MIMS

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Sources
1. Veettil S.K., et al. (2017) Colorectal cancer in Malaysia: Its burden and implications for a multiethnic country. Asian J Surg.;40(6):481–9.
2. Abu Hassan M.R., et al. (2016) Incidence and mortality rates of colorectal cancer in Malaysia. Epidemiol Health;38:e2016007.
3. Lim K.G. (2014) A review of colorectal cancer research in malaysia. Med J Malaysia;69 Suppl A:23–32.
4. Li Z.J., et al. (2010) A novel peptide specifically targeting the vasculature of orthotopic colorectal cancer for imaging detection and drug delivery. J Control Release;148(3):292–302.
5. Lu L., et al. (2017). A novel vascular-targeting peptide for gastric cancer delivers low-dose TNFα to normalize the blood vessels and improve the anti-cancer efficiency of 5-fluorouracil. Peptides;97:54–63.