Recent progress in cancer immunotherapy: Overview of current status and challenges.

Cancer treatment is presently one of the most important challenges in medical science. Surgery, chemotherapy, radiotherapy, or combining these methods is used to eliminate the tumor. Hormone therapy, bone marrow transplantation, stem cell therapy as well as immunotherapy are other well-known therapeutic modalities. Immunotherapy, as the most important complementary method, uses the immune system for treating cancer followed by surgery, chemotherapy, and radiotherapy. This method is systematically used to prevent malignancies development mainly via potentiating antitumor immune cells activation and conversely compromising their exhaustion with the lowest negative effects on healthy cells. Active immunotherapy can be employed for cancer immunotherapy by directly using the ingredients of the immune system and activating immune responses. On the other hand, inactive immunotherapy is utilized by indirect induction and using immune cell-based products consisting of monoclonal antibodies. It has strongly been proved that combination therapy with immunotherapies and other therapeutic means, such as anti-angiogenic agents, could be a rational plan to treat cancer. Herein, we have focused on recent findings concerning the therapeutic merits of cancer therapy using immune checkpoint inhibitors (ICIs), adoptive cell transfer (ACT) and cancer vaccine alone or in combination with other approaches. Also, we offer a glimpse into the current challenges in this context.

Restoration of miR-648 overcomes 5-FU-resistance through targeting ET-1 in gastric cancer cells in-vitro.

BACKGROUND: Endothelin-1 (ET-1) is a peptide overexpressed in gastric cancer (GC) and linked to carcinogenesis and resistance to chemotherapy. Applying microRNAs (miRNAs/miRs) to downregulate ET-1 and reverse resistance to commonly used chemotherapy drugs such as 5-fluorouracil (5-FU) is practical. METHODS: The current study sought to evaluate the miR-648 expression in GC and any plausibility of its replacement, either with or without the combination of chemo agents to downregulate ET-1 expression through interaction with its target gene. To this end, miR-648 and ET-1 expression levels were assessed in GC tissues and adjacent non-tumor tissues driven from 65 patients who had already undergone surgery, fifteen of which had received 5-FU before surgery. The impact of miR-648 and chemo agents on ET-1 expression was measured using qPCR and Western blotting. Further, an MTT assay was conducted to assess its association with cell viability. Ultimately, the association of miR-648 and ET-1 with clinicopathological characteristics was evaluated. RESULTS: The current study revealed that miR-648 was considerably down-regulated, while ET-1 was substantially up-regulated in patients with GC. The 5-FU caused a significant increase in miR-648 and reduced ET-1 expression. It was also determined that overexpression of miR-648 suppressed ET-1 production, notably when combined with 5-FU, leading to survival reduction. These results further showed that miR-648 replacement could sensitize chemoresistant GC cells. Besides, a significant association between ET-1 and miR-648 with clinicopathological features was discovered CONCLUSIONS: miR-648 replacement may serve as a potential oncosuppressive therapeutic approach that warrants further investigation to translate into an effective GC treatment.