Innovative therapeutic strategies for cervical cancer: Advances in pain management, angiogenesis inhibition, and peptide-based therapies

In a study published in the journal of Biofunctional Materials, researchers from Wits Advanced Drug Delivery Platform (WADDP) Research Unit, Department of Pharmacy and Pharmacology, University of the Witwatersrand, Johannesburg have discussed the various challenges faced in the current management of cervical cancer progression and pain. The review also discussed innovative approaches employed to mitigate some of these challenges to improve the quality of life of patients.

Cervical cancer remains the fourth most common cancer in women worldwide, claiming around 350,000 lives and causing 660,000 new cases each year—94 % of them in low- and middle-income countries. Standard surgery, radiotherapy and chemotherapy have improved survival, yet many tumours recur, and treatment-related pain is often severe and complex to manage due to the anatomical location of the cervix. The numerous side effects, including dependence and abuse of opioids which are the main pain medications used is a worrying concern and calls for other alternatives which will be better tolerated. Given these, new therapeutic strategies are being investigated for both tumour suppression effect and pain management properties.

The use of phytocannabinioids like THC (Δ⁹-tetrahydrocannabinol ) and CBD ( Cannabidiol) has gained attention in the management of some cancers as well as pain including cancer related pain. In some Pre-clinical and early-phase clinical studies, phytocannabinoids such as CBD and THC have been shown to act on a network of receptors (CB1, CB2, GPR55, GPR18 and TRPV1) expressed on tumour-innervating nerves and immune cells. Targeting these receptors reduces calcium influx, dampens nociceptive signalling and alleviates cancer pain without the respiratory depression seen with opioids. This could help reduce opioid doses dramatically while still controlling pain with minimal side effects. Although THC has been proven in many studies to be effective in this regard, its psychoactive effect reduces its translation to clinical use. CBD, however, has been found to have no such effects and also proven in some studies to inhibit cancer progression, hence a good candidate for further studies, which could translate to clinical use.

Angiogenesis, the formation of new blood vessels, is fundamental to tumour growth and progression in cervical cancer and targeting this important process has been found to be useful in the fight against cancer progression. The review highlights some anti-angiogenic drugs, particularly targeting VEGF (Vascular Endothelial Growth Factor) amongst others, which have moved from experimental stages to clinical use. Bevacizumab, a VEGF-A–blocking monoclonal antibody, has shown measurable survival benefits in advanced or metastatic cervical cancer. In a Phase II trial, single-agent bevacizumab was well-tolerated and achieved a median progression-free survival of 3.4 months and overall survival of 7.3 months. A larger Phase III study then demonstrated that adding bevacizumab to standard chemotherapy extended median overall survival from 13.3 to 16.8 months, with no harmful rebound effect after stopping treatment. Small-molecule tyrosine-kinase inhibitors targeting VEGFR-2 and emerging agents against the Angiopoietin-Tie2 axis like Apatinib ans Sorafenib amongst others also discussed.

The review also discussed the use of short-chain amino acids to target and bind to specific receptors as well as molecular pathways involved in cancer progression. These protein-based peptides allow for highly specific and low-toxicity treatment. Few of these protein-based peptides have been approved by the FDA for the management of pain and other conditions including cancer. The review discusses various types of peptides with their unique advantages, while Cell-penetrating and tumour-targeting peptides enhance selectivity, self-assembling peptide nanostructures (nanofibres, spheres, tubes or hydrogels) provide stimulus-responsive carriers for drugs, genes or phototherapeutics, improving stability and controlled release. Although challenges remain, including in vivo stability, potential immunogenicity and large-scale manufacturing, peptide platforms generally offer greater biocompatibility and lower systemic toxicity than inorganic metal-based delivery systems, making them an increasingly attractive option for precision oncology.

The paper also discussed various drug delivery systems which are employed in cervical cancer management. Notable amongst them is the use of nanotechnology employing different nanocarriers to deliver chemotherapeutics directly to the cancer site with minimal side effects as well as controlled release. Tumour-microenvironment–responsive systems (acid-cleavable conjugates, furin-triggered liposomes, MOF composites, mesoporous-silica and Mn₃O₄ nanocomposites) were also discussed and found to release payloads only within the acidic, enzyme-rich or oxidative environment of cervical tumours, enabling multi-modal chemo, radio, photo and immunotherapy with markedly lower off-target toxicity. Together, these platforms promise more potent, longer-lasting and better-tolerated treatments for cervical-cancer patients.

This paper was published in Biofuctional Materials (ISSN: 2959-0582), an online multidisciplinary open access journal aiming to provide a peer-reviewed forum for innovation, research and development related to bioactive materials, biomedical materials, bio-inspired materials, bio-fabrications and other bio-functional materials.

The Article Processing Charges (APCs) are entirely waived for papers submitted before the end of 2025.

Citation: Odei-Mensah B, Adeyemi SA, Ngema LM, Mndlovu H, Choonara YE. Innovative therapeutic strategies for cervical cancer: advances in pain management, angiogenesis inhibition, and peptide-based therapies. Biofunct. Mater. 2025(3):0008, https://doi.org/10.55092/bm20250008.