Oncolytic Virotherapy in Peritoneal Metastasis Gastric Cancer: The Challenges and Achievements

Abstract

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death globally. Although the mortality rate in some parts of the world, such as East Asia, is still high, new treatments and lifestyle changes have effectively reduced deaths from this type of cancer. One of the main challenges of this type of cancer is its late diagnosis and poor prognosis. GC patients are usually diagnosed in the advanced stages of the disease, which is often associated with peritoneal metastasis (PM) and significantly reduces survival. This type of metastasis in patients with GC poses a serious challenge due to limitations in common therapies such as surgery and tumor resection, as well as failure to respond to systemic chemotherapy. To solve this problem, researchers have used virotherapy such as reovirus-based anticancer therapy in patients with GC along with PM who are resistant to current chemotherapies because this therapeutic approach is able to overcome immune suppression by activating dendritic cells (DCs) and eventually lead to the intrinsic activity of antitumor effector T cells. This review summarizes the immunopathogenesis of peritoneal metastasis of gastric cancer (PMGC) and the details for using virotherapy as an effective anticancer treatment approach, as well as its challenges and opportunities.

Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases

“… 31 While many types of viruses, including adenoviruses, HSVs, vaccinia virus, Newcastle disease virus, coxsackievirus, measles virus, Seneca Valley virus, poliovirus, parvovirus, vesicular stomatitis virus, and the Maraba virus have been studied for their oncolytic potential, 26 few such as Pexa-Vec, GL-ONC1, vvDD, VAXINIA, and CHECKVacc, are in clinical trials. 4 While OH2 (HSV2) is in a clinical trial for i.p. therapy of patients with PM from all gastrointestinal cancers, there is no successful report of oncolytic virotherapy in the clinical trial of GCPM.…”

“…However, the excitement of the preclinical success of many OVs has yet to be translated into clinically effective therapeutic strategies. 4 While the safety of OVs has been well-established, the results of the early-phase efficacy trials have been disappointing. Most OVs exhibit poor potency, lack tumor selectivity, and generate low tumor response rates.…”

Modulation of Reoviral Cytolysis (I): Combination Therapeutics

“…We also note the potential for different routes of viral administration, such as intraperitoneal or intravascular, or especially for tumors of the gastrointestinal tract, via direct administration orally or as we have shown anally [ 49 ]. As more is learned about the molecular pathways by which oncolytic reovirus kills many cancer cell types, while sparing normal cells and tissues, the rational combination of more potent agents or immunomodulators ([ 50 , 51 , 52 , 53 , 54 ]; also Kubota et al, submitted) plus the potential for engineered virus [ 55 ] with greater anticancer action and reduced side effects will become clearer. Finally, we return to the observation that we ( Figure 1 ) and others have made, which is that the correlation between Ras activation and reoviral responsiveness is unexpectedly poor.…”

Emerging therapeutic approaches for peritoneal metastases from gastrointestinal cancers

“…Considering the insufficient results of the current treatment of PM, new or improved treatments are needed. 55 , 56 In this section, we report novel treatment strategies, including oncolytic viral approaches, , cellular therapies, nanotherapeutic agents, and biologics.…”