The Use of Carbon Fiber-Reinforced Instrumentation in Patients with Spinal Oncologic Tumors: A Systematic Review of Literature and Future Directions.

INTRODUCTION: Metastatic spine tumors affect over 30% of patients who have been diagnosed with cancer. While techniques in surgical intervention have undoubtedly evolved, there are some pitfalls when spinal instrumentation is required for stabilization following tumor resection. However, the use of carbon fiber-reinforced polyetheretherketone (CFR-PEEK) implants has become increasingly popular due to improved radiolucency and positive osteobiologic properties. Here, we present a systematic review describing the use of CFR-PEEK-coated instrumentation in the oncologic population while identifying advantages and potential shortcomings of these devices. METHODS: In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, a systematic review was conducted in March 2022 to identify articles detailing the use of CFR-PEEK implants for spinal instrumentation in patients with primary and secondary spine tumors. The search was performed using the PubMed, Scopus, and Embase databases. RESULTS: An initial search returned a total of 85 articles among the three databases used. After the exclusion of duplicates and screening of abstracts, 21 full-text articles were examined for eligibility. Eleven articles were excluded due to not fitting our inclusion and exclusion criteria. Ten articles were subsequently eligible for full-text review. CONCLUSIONS: CFR-PEEK possesses a similar safety and efficacy profile to titanium implants but has distinct advantages. It limits artifact, increases early detection of local tumor recurrence, increases radiotherapy dose accuracy, and is associated with low complication rates (9.96%)-making it a promising alternative for the demands unique to the treatment/outcome of spinal oncologic patients.

Characterization and Treatment of Spinal Tumors.

The prevalence of spinal tumors is rare in comparison to brain tumors which encompass most central nervous system tumors. Tumors of the spine can be divided into primary and metastatic tumors with the latter being the most common presentation. Primary tumors are subdivided based on their location on the spinal column and in the spinal cord into intramedullary, intradural extramedullary, and primary bone tumors. Back pain is a common presentation in spine cancer patients; however, other radicular pain may be present. Magnetic resonance imaging (MRI) is the imaging modality of choice for intradural extramedullary and intramedullary tumors. Plain radiographs are used in the initial diagnosis of primary bone tumors while Computed tomography (CT) and MRI may often be necessary for further characterization. Complete surgical resection is the treatment of choice for spinal tumors and may be curative for well circumscribed lesions. However, intralesional resection along with adjuvant radiation and chemotherapy can be indicated for patients that would experience increased morbidity from damage to nearby neurological structures caused by resection with wide margins. Even with the current treatment options, the prognosis for aggressive spinal cancer remains poor. Advances in novel treatments including molecular targeting, immunotherapy and stem cell therapy provide the potential for greater control of malignant and metastatic tumors of the spine.

Effects of Lovastatin on Brain Cancer Cells.

Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for brain tumors includes surgery, radiotherapy, and chemotherapy. However, resistance to treatment remains a problem with recurrence shortly following. The resistance to treatment may be caused by cancer stem cells (CSCs), a subset of brain tumor cells with the affinity for self-renewal and differentiation into multiple cell lineages. An emerging approach to targeting CSCs in brain tumors is through repurposing the lipid-lowering medication, lovastatin. Lovastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that impacts the mevalonate pathway. The inhibition of intermediates in the mevalonate pathway affects signaling cascades and oncogenes associated with brain tumor stem cells (BTSC). In this review, we show the possible mechanisms where lovastatin can target BTSC for different varieties of malignant brain tumors.

Lovastatin Inhibits RhoA to Suppress Canonical Wnt/ß-Catenin Signaling and Alternative Wnt-YAP/TAZ Signaling in Colon Cancer.

Statins are first-line drugs used to control patient lipid levels, but there is recent evidence that statin treatment can lower colorectal cancer (CRC) incidence by 50% and prolong CRC patient survival through mechanisms that are poorly understood. In this study, we found that the treatment of APCmin mice by the mevalonate pathway inhibitor lovastatin significantly reduced the number of colonic masses and improved hypersplenism and peripheral anemia. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) analysis of colonic mass tissues showed a potent inhibitory effect in both Wnt/ß-catenin signaling and YAP/TAZ signaling in the lovastatin treatment group. The results of our transcriptomic analyses in RKO indicated that lovastatin regulated several proliferation-related signaling pathways. Moreover, lovastatin suppressed important genes and proteins related to the canonical Wnt/ß-catenin and alternative Wnt-YAP/TAZ signaling pathways in RKO and SW480 cells, and these effects were rescued by mevalonic acid (MVA), as confirmed through a series of Western blotting, RT-PCR, and reporter assays. Given that statins suppress oncogenic processes primarily through the inhibition of Rho GTPase in the mevalonate pathway, we speculate that lovastatin can inhibit certain Rho GTPases to suppress both canonical Wnt/ß-catenin signaling and alternative Wnt-YAP/TAZ signaling. In RKO cells, lovastatin showed similar inhibitory properties as the RhoA inhibitor CCG1423, being able to inhibit ß-catenin, TAZ, and p-LATS1 protein activity. Our results revealed that lovastatin inhibited RhoA activity, thereby suppressing the downstream canonical Wnt/ß-catenin and alternative Wnt-YAP/TAZ pathways in colon cancer cells. These inhibitory properties suggest the promise of statins as a treatment for CRC. Altogether, the present findings support the potential clinical use of statins in non-cardiovascular contexts and highlight novel targets for anticancer treatments.