## 1 Introduction  
The mevalonate pathway represents the most important metabolic pathway of the cell system for synthesizing bioactive molecules involved in growth control or the synthesis of cholesterol [1]. Furthermore, the existence of several pathological conditions [2; 3; 4] due to defects in the pathway is proof of its importance. Although the main regulatory point in the mevalonate pathway is 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), one of the most highly regulated enzymes in the body [1; 5], the FPPS enzyme plays a crucial role in the pathway. In fact, after the mevalonate is converted to isopentenyl pyrophosphate (IPP) by the action of a cascade of three enzymes, FPPS combines the GPP (geranylpyrophosphate) with another molecule of IPP to produce farnesyl pyrophosphate (FPP). This further reacts with IPP to form geranylgeranyl pyrophosphate (GGPP). While FPP is a major branch-point precursor for sterols with an end-point in cholesterol production, FPP, together with GGPP, is the focal point in the non-sterol branch, which is the basis of post-translational modifications of small GTP-binding proteins (Ras, RhoA, Rac, etc.) [6]. The mevalonate pathway is an attractive target in many therapeutic research areas concerning autoimmune disorders, atherosclerosis, and Alzheimer's disease [7]. The manipulation of this pathway results in alteration of malignant cell growth with promising potential for application in human cancers [8]. Indeed, several pharmacological options block the mevalonate pathway in cancer cells, such as statins and amino-bisphosphonates (N-BPs). The former inhibits the early phase of the pathway, and the latter inhibits the FPP synthase enzyme, inducing cell cycle arrest, apoptosis, inhibition of protein prenylation, and cholesterol reduction [9; 10; 11; 12; 13; 14]. Mevalonate pathway inhibitors, in combinations among themselves and with cytotoxic drugs, represent a promising approach to enhancing the efficacy of anticancer therapies [8]. Three generations of BPs with increasing anti-resorptive potency have been successively developed. The most active compound of this class is zoledronic acid (ZA), which is up to 10,000 fold more potent than first-generation compounds and has been used successfully in clinical applications [15]. The research about the pharmacokinetics of BPs administered as drugs have demonstrated that BPs, in blood, are bound to albumin and are quickly cleared from plasma, with about 50 percent deposited in bone and the remaining part excreted in the urine. Tumor cells uptake BPs very rapidly by fluid-phase endocytic internalization [16], and in parallel, they bind to Ca\({}^{2+}\)-containing bone mineral surfaces at sites of active bone remodeling [17; 18]. After bone resorption, osteoclasts take BPs in endocytic vacuoles [19], and their acidification, together with the assembly of the complex ATRAID-SLC37A3, are required for BPs to enter the cytosol, thereby allowing either the diffusion or transport of BPs across the vesicular membrane [16; 20]. When zoledronic acid (ZA) is in the cytosol, it binds FPPS, thus inhibiting the transformation of the early metabolites of the mevalonate pathway (IPP) in GPP, resulting in the accumulation of IPP [21] and its isomer DMAPP [22]. ZA shows an immunomodulatory effect on the immune system and is being widely discussed in this pandemic period (COVID-19). Indeed, as an immunosutaminant, it boosts anti-viral and anti-tumoral \(\gamma\delta\) T cell expansion thanks to the accumulation of IPP [23]. At the same time, it could act on dendritic cells (DC) to stimulate the immune response by modifying the expression of functional markers such as CD83, HLADR, and CD80 [24]. The exact mechanisms through which V\(\gamma\)9V\(\delta\)2 T cells become activated by IPP are a recent topic of investigations [25; 26].