Researchers at the University of Illinois, Urbana-Champaign, have discovered a novel approach to combating leukaemia through the use of drug-carrying DNA aptamers. These short strands of DNA function similarly to small projectiles. Leukaemia stem cells are identified and targeted, as these cells frequently contribute to the recurrence of cancer following treatment. The recent study indicates that these aptamers deliver cancer-fighting drugs and have a detrimental effect on cancer stem cells independently.

The research was conducted under the leadership of Professor Xing Wang, who holds positions in bioengineering and chemistry at the university. The results were published by his team in the journal Advanced Functional Materials. The researchers indicate that numerous existing therapies for blood cancers, such as leukaemia, exhibit limited effectiveness due to the ability of cancer cells to migrate throughout the body and conceal themselves within the bone marrow. The accessibility of these hiding cells poses challenges for conventional treatments. Leukaemia frequently recurs despite treatment efforts.

Dr Wang stated that this research illustrates a method for addressing the fundamental causes of leukaemia. Targeted cancer treatments frequently encounter issues related to toxicity and efficacy. The aptamers are designed to specifically target and effectively eliminate these stem cells. The research emphasises targeting the specific cells responsible for relapse rather than solely addressing the overall tumour mass. 

Leukaemia and other blood cancers present significant treatment challenges due to the widespread distribution of cancer cells throughout the body. Abhisek Dwivedy, the first author of the study, noted that cancer stem cells in leukaemia exhibit deceptive characteristics. They can reside in the bone marrow and are resistant to conventional medications. Dwivedy emphasised the importance of targeting and eliminating stem cells in cases of leukaemia, lymphoma, or other blood cancers. He noted that the presence of any remaining stem cells poses a risk for relapse and the development of secondary cancers. 

The research team identified specific DNA aptamers capable of targeting markers present on the surfaces of acute myeloid leukaemia stem cells. The researchers subsequently combined these aptamers with daunorubicin, a drug recognised for its effectiveness in treating leukaemia. The aptamers transport the drug to the cancer cells, where they subsequently release it to ensure its effective action. Dwivedy stated, “This is particularly significant for drugs such as daunorubicin, as the drug alone faces challenges in crossing the cell membrane.” Aptamers have the capability to transport it effectively. 

The study reveals that the simultaneous targeting of two markers significantly outperforms the targeting of a single marker. Professor Wang stated, “Our study demonstrates that having two targets enhances selectivity compared to having just one.” Antibody-drug conjugates for blood cancers have been developed to target a specific marker; however, this marker is also present on numerous healthy cells. There is a significant amount of toxicity linked to antibody conjugates. Two targets were used: a combination frequently observed in leukaemia cancer cells and leukaemia stem cells. The combination of the two provides a clearly defined objective. 

The researchers conducted tests on drug-carrying aptamers using leukaemia cells in laboratory settings as well as in mouse models. Lab tests indicated that the aptamer alone achieved a 40 per percent reduction in cancer cells within a 72-hour period. The effective dose of daunorubicin, when administered via aptamers, was significantly lower than the standard dosage typically required. The treatment demonstrated effectiveness in mice with leukaemia, utilising only one-tenth of the standard drug dosage; no adverse effects were observed beyond the targeted cells. Professor Wang stated, “This was exciting to us, because in cancer research, what we observe in vitro does not always correlate with what occurs in the body.” In the study, mice given aptamer-drug conjugates showed a big increase in survival and a decrease in tumours, achieving these results with just one-tenth of the usual dose and without any side effects. 

This new approach presents potential for improved and more cost-effective leukaemia treatments in countries such as India. The use of reduced drug dosages that specifically target cancer cells results in a decrease in side effects and a diminished need for costly medical care. This method has the potential to make advanced cancer treatment accessible to numerous patients in resource-limited environments.