Cervical cancer continues to afflict hundreds of thousands of women worldwide each year, disproportionately impacting those in low- and middle-income countries where access to effective care remains limited. Despite the availability of conventional treatments such as surgery, chemotherapy, and radiotherapy, the management of cervical cancer progression and the associated pain remains an intricate challenge for clinicians. Tumour recurrence and the debilitating pain caused by tumour invasion into adjacent anatomical structures often compromise patient quality of life. Moreover, reliance on opioid analgesics exacerbates treatment complications owing to side effects and potential for misuse. Recent research is therefore intensifying its focus on novel therapeutic avenues that not only inhibit tumour growth but also address the multifaceted nature of cancer pain with enhanced specificity and reduced toxicity.
A promising strategy discussed in a comprehensive review from researchers at the Wits Advanced Drug Delivery Platform (WADDP) Research Unit involves harnessing the analgesic and antineoplastic potential of phytocannabinoids such as cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). These plant-derived cannabinoids engage a complex receptor network including CB1, CB2, GPR55, GPR18, and TRPV1, all expressed on tumour-innervating nerves and immune cells within the tumour microenvironment. Through modulation of calcium ion influx and subsequent attenuation of nociceptive signaling, these agents provide analgesia without the adverse respiratory depression commonly associated with opioid use. Although THC’s psychoactive properties limit its clinical applicability, CBD offers a favorable safety profile and has demonstrated inhibitory effects on tumour progression in preclinical models, making it a compelling candidate for translational development.
Angiogenesis, the physiological process of new blood vessel formation, stands as a critical driver of tumour sustenance and expansion in cervical cancer. Targeting angiogenic pathways—specifically the vascular endothelial growth factor (VEGF) axis—has thus garnered considerable attention. The monoclonal antibody bevacizumab, which binds to VEGF-A, has transitioned from experimental use to become an integral component of advanced cervical cancer therapy. Clinical trials have underscored its efficacy; a Phase II study reported a median progression-free survival of 3.4 months with manageable toxicity, while a subsequent Phase III trial revealed that combining bevacizumab with chemotherapy extended median overall survival by over three months compared to chemotherapy alone. Additionally, small-molecule tyrosine kinase inhibitors targeting VEGF receptor 2 (VEGFR-2), such as apatinib and sorafenib, have emerged as adjunctive agents, offering alternative or complementary mechanisms to suppress tumour vascularization.
Beyond angiogenesis inhibition, innovative peptide-based therapies are being explored for their unique ability to achieve precision targeting of tumour cells while minimizing systemic toxicity. Short-chain amino acid peptides, capable of engaging defined molecular receptors and pathways involved in cancer proliferation, offer a versatile platform for drug delivery and therapeutic intervention. Cell-penetrating peptides and tumour-targeting peptides enhance selective uptake by neoplastic cells, facilitating localized drug action. Furthermore, self-assembling peptides can form nanostructures—including nanofibres, spheres, tubes, and hydrogels—that serve as stimulus-responsive carriers for chemotherapeutics, gene therapies, or phototherapeutic agents. These nanostructures improve stability, enable controlled release, and can be engineered to respond to specific tumour microenvironment conditions, such as pH or enzymatic activity, enhancing treatment specificity.
Nanotechnology-driven drug delivery systems constitute another frontier in cervical cancer therapy. By leveraging nanocarriers capable of selective accumulation at the tumour site, these systems reduce systemic exposure and adverse effects of chemotherapeutic agents. Advanced tumour microenvironment–responsive platforms, including acid-cleavable conjugates, furin enzyme-triggered liposomes, metal-organic framework (MOF) composites, mesoporous silica nanoparticles, and Mn₃O₄ nanocomposites, facilitate payload release only under the acidic, enzyme-rich, and oxidative conditions characteristic of cervical tumours. This localized release paradigm enables multimodal therapeutic approaches intertwining chemotherapy, radiotherapy, phototherapy, and immunotherapy. The combined effect enhances antitumour efficacy while markedly lowering off-target toxicity that commonly hampers conventional systemic treatments.
A critical and understudied aspect of cervical cancer care involves effective pain management. The anatomical complexity of the cervix, coupled with tumour infiltration and treatment-related tissue damage, leads to severe nociceptive and neuropathic pain often refractory to standard analgesics. The integration of cannabinoids offers a novel pharmacological approach, targeting peripheral and central nociceptive pathways while circumventing opioid-associated risks. Preclinical investigations highlight the role of G protein-coupled receptors and transient receptor potential channels in mediating cannabinoid analgesia, offering a mechanistic basis for developing non-opioid analgesics that could revolutionize supportive cancer care.
The review stresses that despite the promise of these innovative therapies, significant challenges remain before clinical translation can be fully realized. Peptide therapeutics face hurdles including in vivo stability, immunogenicity risks, and scalable manufacturing complexity. Similarly, nanocarrier systems must overcome biological barriers such as mononuclear phagocyte system clearance, potential cytotoxicity of nanomaterials, and precise control over drug loading and release kinetics. Robust preclinical validation paired with well-designed clinical trials is paramount to address these translational gaps.
Furthermore, the multidisciplinary nature of cervical cancer management underscores the need for integrated therapeutic regimens combining tumour suppression, antiangiogenic strategies, and analgesic innovation. Personalized medicine approaches, leveraging molecular profiling and nanotechnology, could tailor interventions to individual tumour biology and patient-specific pain phenotypes, optimizing efficacy while minimizing side effects. The deployment of smart drug delivery systems responsive to the unique tumour microenvironment paves the way for next-generation therapies with enhanced precision.
The social and economic burden of cervical cancer, especially in resource-limited settings where the majority of cases occur, demands treatment paradigms balancing effectiveness, accessibility, and tolerability. Innovations highlighted in this review, including non-psychoactive cannabinoids and peptide-mediated drug delivery, offer scalable and potentially cost-effective solutions if integrated thoughtfully into existing healthcare infrastructures. Collaborative efforts among researchers, clinicians, regulatory bodies, and patient advocacy groups will be essential to translate laboratory discoveries into measurable public health gains.
Overall, this comprehensive examination of emerging therapeutic modalities marks a pivotal step toward reimagining cervical cancer care. By targeting both tumour biology and patient quality of life through pain alleviation, angiogenesis inhibition, and precision peptide therapies, the oncology field moves closer to transforming cervical cancer from a formidable adversary into a manageable chronic condition.
This investigative review published in Biofunctional Materials (ISSN: 2959-0582), an open-access multidisciplinary journal committed to advancing bioactive material sciences, outlines these advances with an eye toward future clinical application. Importantly, to encourage continued groundbreaking research, the journal currently waives article processing charges for submissions received before the end of 2025.
As the landscape of cervical cancer therapeutics evolves, integrating molecular pharmacology with innovative biomaterial engineering promises substantial improvements in patient outcomes and sustainable, targeted treatment frameworks. This radical shift is poised to redefine the standards of care for one of the world’s most prevalent and deadly female cancers.
Subject of Research: Not applicable
Article Title: Innovative therapeutic strategies for cervical cancer: advances in pain management, angiogenesis inhibition, and peptide-based therapies
News Publication Date: 7-May-2025
Web References: http://dx.doi.org/10.55092/bm20250008
References: 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
Image Credits: Beatrice Odei-Mensah, Samson A. Adeyemi, Lindokuhle M. Ngema, Hillary Mndlovu, Yahya E. Choonara; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
Keywords: Cervical cancer
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