Researchers trial cancer drugs that spare the heart

Maltese researchers are studying ways to reduce the heart-related side effects of some anti-cancer therapies.

They are studying a new drug combination in the lab, using what are often referred to as mini heart models grown in a tube, or more scientifically as 3D tissue models.

The aim of the research project is to provide alternative treatments that can attack cancer cells while minimising heart side-effects, said principal investigator Dr Vanessa Petroni Magri.

Harm to the heart is known to be a side effect of certain anti-cancer medication, such as chemotherapy, and the Lung Cancer Research Malta team, in collaboration with major foreign research centres in Ireland, France and Portugal, are working on whether an innovative triple chemotherapeutic strategy could not help manage certain cancers more effectively while reducing knock-on effects.

“Certain chemotherapeutic drugs are very effective in killing off the cancer but are known to have side effects such as cardiotoxicity,” Petroni Magri explained. “Most anti-cancer drugs, especially those used in cases of aggressive tumours, may give a good patient response but often also produce toxicity. In the longer term, the patient may sometimes become resistant to these drugs after a couple of cycles.”

The university resident academic, specialised in molecular oncology, says overcoming resistance is a constant battle in the cancer world. “But through our triple combinatory approach, we are trying to overcome both toxicity, in this case, to the heart, as well as resistance to treatment.”

The LCRM research group, headed by Petroni Magri and Prof. Anthony Fenech at the department of Clinical Pharmacology and Therapeutics in the Faculty of Medicine and Surgery, has been working on this new therapeutic combination for the past 10 years.

Two of the three drugs being used are ‘special’

“Two of the three drugs being used are ‘special’ in that they target specific defective genes that would eventually lead to an aggressive tumour, such as lung cancer. These drugs influence the cell’s genetic processes, causing them to drastically reduce production of selected unwanted proteins and preventing the tumour from becoming more aggressive,” Petroni Magri explained.

The third drug in the combination targets proteins that have already been produced, reducing tumour growth.

“The rationale of the treatment is twofold. The reasoning also follows the logic that when a patient is given three drugs instead of one, the concentration of each can be reduced and, therefore, the side effects would also be expected to be less,” she continued.

The drugs were supplied by the other research centres and the local team studied the pathways and oncological mechanisms to determine the most effective way to combine them, said Petroni Magri.

Now, LCRM is investigating whether this innovative triple therapy combination is associated with any damage to the heart tissue.

The next step would be for the triple therapy to be tested on animals but the team is also 'excited' to be building mini heart tissue models on which to study it before

Funding from the NGO Beating Hearts Malta, received through the RIDT – University of Malta Research Trust, means experiments can kick off in the coming months.

The next step would be for the triple therapy to be tested on animals but the team is also “excited” to be building mini heart tissue models on which to study it before.

Petroni Magri’s team, whose focus is molecular oncology, has been testing the therapy on mini organs in a tube and is currently building different mini lung tissue models in the lab.

“If you slice a properly prepared mini organ, and look at it under a microscope, the tissue is practically exactly like what you would find in a human,” she said.

“A good chunk of the funding will go into building the mini heart structures in the lab,” she said.

“Following testing for cardiotoxicity on the mini heart models, the experimentation will move onto zebra fish before other small mammals, and, hopefully, eventually clinical trials on patients,” Petroni Magri said.

“However, any human trials are a very long distance away and extensive testing on the safety and effectiveness has to be carried out before these can even be considered.”