RE:Oncolytic Virus in Triple Negative Breast Cancer (TNBC)Repost from June 2022 -
Breast cancer has a high prevalence rate and the highest mortality rate in women. Breast cancer can be divided into the molecular types—luminal A, luminal B, ERBB2+, and triple negative breast cancer (TNBC)—based on different expression profiles of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
TNBC is found in approximately 15% of breast cancer patients and is characterized by no expression of ER and PR as well as no amplification of the HER2 gene. TNBC has a more aggressive clinical course, greater tendency to metastasize to other organs, higher risk of distant recurrence, earlier recurrence, and poor prognosis than other forms of breast cancer].
Currently, commonly used clinical treatment methods, such as surgery, radiotherapy, and chemotherapy, have not achieved a satisfactory outcome for this cancer subtype.
Although a better pathologic complete response rate can be achieved by neoadjuvant chemotherapy, overall prognosis remains poor. Hence, new targets of TNBC have been studied, however, no success has yet been reported in clinical practice. Currently, the treatment approach primarily relies on conventional chemotherapy. However, disease progression, metastasis, or recurrence occurs due to the occurrence of chemotherapeutic drug resistance. Specifically, P-glycoprotein (P-gp), multidrug-resistant protein-1 (MRP1), and breast cancer resistance protein (BCRP) contribute to the development of chemotherapeutic resistance by increasing drug efflux and, subsequently, TNBC metabolism, leading to the replacement of the chemotherapeutic agents cannot benefit patients more. Hence, an urgent need exists for the development of novel treatment strategies for TNBC.
Oncolytic virotherapy may represent one such strategy for patients presenting with chemotherapeutic drug resistance. Furthermore, combination oncolytic viral therapy may be effective for TNBC patients who have undergone immunotherapy with poor outcomes as this strategy facilitates activation of the immune response via OV infection.
Additionally, TNBC patients with poor physical conditions who are unable to tolerate surgical radiotherapy or chemotherapy may be candidates for oncolytic virotherapy as these viruses have been shown to elicit minimal impairment of healthy bystander cells with few adverse side effects."
Also
Tumors with non-infiltrates corresponding to Immunoscore I0 are designated as ‘cold’ tumors, while highly infiltrated tumors corresponding to Immunoscore I4 are called ‘hot’ tumors .
Due to the lack of immune cells in the tumor microenvironment (TME), ‘cold’ tumors are not sensitive to immune response, a characteristic that is responsible for the unsatisfactory effect of several treatment methods in these types of tumors. However, OVs can override this condition. That is, following OV infection, the immune response first recruits neutrophils and macrophages to eliminate the OVs and infected cells. Meanwhile, DCs sense viral PAMPs and produce type I IFNs capable of directly activating NK cells, which subsequently produce IFN-γ and TNF-α to further activate and recruit macrophages, DCs and T cells. Since OVs have a greater propensity to infect tumor cells, these responses ultimately result in the infiltration of immune cells to the tumor microenvironment (TME). Thus, ‘cold’ tumors become ‘heated,’ enhancing the antitumor immune response.
[Since June 2020 ONCY has demonstrated through the AWARE-1 WOO study that pelareorep is able to remodel the TME, while activating the innate and adaptive immune system and while stimulating the interferon gamma pathway which leads to the down-regulation of HIF-1a and the down-regulation of the catalyst adenosine, which happens to be is a potent immunosuppressant in he TME]
https://biomarkerres.biomedcentral.com/articles/10.1186/s40364-021-00318-4