During tumour development, cancer cells do not exist in isolation; rather, they interact with a diverse array of cellular and non-cellular components that collectively form a unique ecosystem known as the tumour microenvironment (TME).

Found in the journal, Results in Chemistry.

This highly complex environment provides optimal conditions for tumour growth and progression, playing a pivotal role in both cancer development and treatment response.

In recent years, growing recognition of the TME’s significance as a biological target—particularly its role in tumour resistance—has positioned it at the forefront of research efforts.

Understanding its mechanisms has become essential for developing innovative therapeutic strategies aimed at overcoming resistance and improving treatment efficacy.

A team from the Universitat Jaume I in Castelló, led by researcher Eva Falomir Ventura, coordinator of the Chemistry for Medicine (JMC) group, has achieved promising results in testing molecules previously designed and synthesised by the same group.

These molecules have the potential to block cancer cell growth by altering key microenvironment properties, such as immunity, inflammation, and the formation of new blood vessels.

In the different studies they are carrying out in the project ‘Development of new multi-target anti-cancer agents with a potential disruptive effect on the tumour microenvironment’, funded by the State Research Agency of the 2021-2023 State Plan for Scientific, Technical and Innovation Research, which ends in September 2025, the research team has synthesised and biologically evaluated more than a hundred small organic molecules of the aryltriazole and tetrazole types, of the styrene and styrylurea or styrylcarbamate derivatives types.

Preliminary results have shown, for example, that compounds with a tetrazole or triazole template are not at all toxic in themselves, but have the capacity to block the growth of cancer cells when these are in the presence of defensive cells such as T cells or monocytes.

It has been proven that, in vitro, some of these compounds are capable of modulating inflammation, reducing the presence of pro-inflammatory cytokines in MT and stimulating immunological capacity, activating defensive cells against tumours.

In addition, some of them have been shown to be selective in differentiating cancer cells from healthy cells and promoting apoptosis (programmed death) of bad cells.

In some of these compounds designed by the group, in vitro experimentation suggests that they are molecules with inhibitory capacities on two of the proteins that play a crucial role in the spread of cancer (VEGFR-2, responsible for the creation of new blood vessels and the spread of cancer cells, and PD-L1, which helps cancer to evade the immune system).

Some of these molecules have been shown to increase the activity of CD8+ T immune cells, which are crucial in the fight against this disease.

These findings suggest the potential of these new compounds, although further research is needed to explore the detailed mechanisms of action, optimise their potency and selectivity, and evaluate their efficacy in preclinical and clinical models before they can be developed into therapeutic agents for the treatment of cancer.

During the development of the project, the research team (made up of Eva Falomir, Pedro Miguel Carda, Amelia Bou Puerto, Raquel Gil Edo, Alberto Pla López and Celia Martín Beltrán) has opened up new channels of collaboration with other groups at the UJI (SUPRAMAT, GROC) for the application of materials such as hydrogels or nanoparticles, Sustainable and Supramolecular Chemistry, Computational Biochemistry, MicroBIO and Biochemistry and Biotechnology, who are also studying these compounds and their relationship with biological targets.

Cooperation has also been extended to other European centres, such as the Medical School of Edinburgh (United Kingdom), to carry out more exhaustive studies on the influence of the compounds on onco-inflammatory processes, or the University of Leuven (Belgium), which analyses the antiviral and antitumour properties of the compounds obtained at the UJI.

In order to carry out the analysis and study of all the compounds and elements and their interaction with human cancer cell lines (colon, breast or lung), in addition to the group's own laboratories, the NMR, mass spectrometry and flow cytometry facilities of the UJI's Central Scientific Instrumentation Service, which has an advanced scientific infrastructure, have been used.

Source: Universitat Jaume I