Synergistic Potential of Antibiotics with Cancer Treatments

Abstract

Intratumoral microbiota, the diverse community of microorganisms residing within tumor tissues, represent an emerging and intriguing field in cancer biology. These microbial populations are distinct from the well-studied gut microbiota, offering novel insights into tumor biology, cancer progression, and potential therapeutic interventions. Recent studies have explored the use of certain antibiotics to modulate intratumoral microbiota and enhance the efficacy of cancer therapies, showing promising results. Antibiotics can alter intratumoral microbiota's composition, which may have a major role in promoting cancer progression and immune evasion. Certain bacteria within tumors can promote immunosuppression and resistance to therapies. By targeting these bacteria, antibiotics can help create a more favorable environment for chemotherapy, targeted therapy, and immunotherapy to act effectively. Some bacteria within the tumor microenvironment produce immunosuppressive molecules that inhibit the activity of immune cells. The combination of antibiotics and other cancer therapies holds significant promise for creating a synergistic effect and enhancing the immune response against cancer. In this review, we analyze several preclinical studies that have been conducted to demonstrate the synergy between antibiotics and other cancer therapies and discuss possible clinical implications.

Keywords: antibiotics; chemotherapy; immunotherapy; microbiome; microbiota; radiotherapy.

Figure 2

Ciprofloxacin novel derivatives with remarkable anticancer activity are mediated by high-affinity interaction with Topoisomerase enzymes. Reproduced with permission from https://www.mdpi.com/1420-3049/29/22/5382 [52]. Accessed on 20 December 2024.

Figure 5

Autophagy induced by Tetracyclines and Macrolides synergize with Tyrosine Kinase Inhibition, tilting the balance toward cancer cell death instead of cancer cell resistance to antiproliferative agents. Reproduced with permission from https://www.mdpi.com/2072-6694/16/17/2989 [98]. Accessed on 20 December 2024.

Figure 1

Main common antibiotic classes and specific molecules involved in this study. Their bioavailability in various body districts and complex interaction with different compositions of local microbiota make it very difficult to predict their antitumor and systemic effects. Preclinical and clinical evidence has therefore been empirically reviewed.

Figure 3

Doxycyclin and azithromycin inhibition of mitochondrial activity leads to increased ROS production, inducing DNA damage and apoptosis in cancer stem cells. These effects can be further potentiated by various substances, such as vitamin C. Reproduced with permission from https://www.mdpi.com/2218-273X/10/1/79 [75]. Accessed on 20 December 2024.

Figure 4

Schematic representing a chemotherapeutic drug approach to targeting cancer stem cells (CSCs) as a potential treatment for cancer. Salinomycin has shown specific preclinical activity against CSCs. Reproduced with permission from https://www.mdpi.com/2673-8937/3/2/16 [91]. Accessed on 20 December 2024.

Figure 6

Schematic representation of the multi-epitope-based vaccine designed by linking the MHC-I and MHC-II epitopes of F. nucleatum with the different linkers and adjuvant. Reproduced with permission from https://www.mdpi.com/2076-393X/11/3/525 [108]. Accessed on 20 December 2024.