The Evolution and Future of Targeted Cancer Therapy: From Nanoparticles, Oncolytic Viruses, and Oncolytic Bacteria to the Treatment of Solid Tumors

Abstract

While many classes of chemotherapeutic agents exist to treat solid tumors, few can generate a lasting response without substantial off-target toxicity despite significant scientific advancements and investments. In this review, the paths of development for nanoparticles, oncolytic viruses, and oncolytic bacteria over the last 20 years of research towards clinical translation and acceptance as novel cancer therapeutics are compared. Novel nanoparticle, oncolytic virus, and oncolytic bacteria therapies all start with a common goal of accomplishing therapeutic drug activity or delivery to a specific site while avoiding off-target effects, with overlapping methodology between all three modalities. Indeed, the degree of overlap is substantial enough that breakthroughs in one therapeutic could have considerable implications on the progression of the other two. Each oncotherapeutic modality has accomplished clinical translation, successfully overcoming the potential pitfalls promising therapeutics face. However, once studies enter clinical trials, the data all but disappears, leaving pre-clinical researchers largely in the dark. Overall, the creativity, flexibility, and innovation of these modalities for solid tumor treatments are greatly encouraging, and usher in a new age of pharmaceutical development.

Hacking the Immune Response to Solid Tumors: Harnessing the Anti-Cancer Capacities of Oncolytic Bacteria

“…Several C. sporogenes strains have been genetically modified to incorporate therapeutic proteins with a specific focus on enzymes that sensitize the tumor to specific chemotherapeutic agents with thorough reviews found elsewhere in the literature [ 229 , 257 , 298 , 299 ], as has their progress toward clinical translation [ 57 ]. This allows for both specific targeting to tumor cells exclusively, as well as potent ‘bystander’ effects as nearby tumor cells are also exposed to the therapeutic drug [ 300 ].…”

“…Ultimately, this creates an environment that is hostile to cancer cells while promoting the activation of immune cells that can attack the tumor as previously reviewed [ 56 ]. Clostridium novyi -NT, for example, is theorized to utilize LPS to stimulate the innate immune response [ 57 ]. In this context, LPS is hypothesized to trigger the release of pro-inflammatory cytokines, leading to the activation of immune cells and the recruitment of immune cells to the site of the tumor, as previously reviewed [ 57 ].…”

“…Clostridium novyi -NT, for example, is theorized to utilize LPS to stimulate the innate immune response [ 57 ]. In this context, LPS is hypothesized to trigger the release of pro-inflammatory cytokines, leading to the activation of immune cells and the recruitment of immune cells to the site of the tumor, as previously reviewed [ 57 ]. A detailed discussion on individual oncolytic bacterial species and their interactions with the aforementioned components follows in their respective sections below.…”

Nanotechnology for Pediatric Retinoblastoma Therapy

“…In Table 3 the combination studies of nanoparticles drug therapy with other effective therapies against RB are summarized. Finally, it is necessary to mention the last frontier of RB treatment which involved the use of oncolytic viral vectors that can be included in the nanomedicine approach [33,99,100].…”

A New Paradigm in Cancer Treatment: Identifying and Targeting Clonal Mutations

“…Finally, there is one FDA-approved oncolytic bacterial vector that is used to treat (early-stage) non-muscle invasive bladder cancer, Bacillus Calmette-Guérin (BCG) [12]. It is an attenuated strain Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s).…”