Mitochondria play pivotal roles in most eukaryotic cells, ranging from energy production to regulation of apoptosis. As sites of cellular respiration, mitochondria experience accumulation of reactive oxygen species (ROS) due to damage in electron transport chain carriers. Mutations in mitochondrial DNA (mtDNA) as well as nuclear DNA (nDNA) are reported in various cancers. Mitochondria have a dual role in cancer: the development of tumors due to mutations in mitochondrial genome and the generation of ROS. Impairment in the mitochondria-regulated apoptosis pathway accelerates tumorigenesis. Numerous strategies targeting mitochondria have been developed to induce the mitochondrial (i.e., intrinsic) apoptosis pathway in cancer cells. This review elaborates the roles of mitochondria in cancer with respect to mutations and apoptosis, and discusses mitochondria-targeting strategies as cancer therapies to enhance the killing of cancer cells.

Cancer stem cells (CSCs) are one of the reasons for the relapse of cancer cells and metastasis. They have drug resistance against most chemotherapeutic agents. CSCs are also responsible for tumor cell heterogeneity and cause minimal residual disease. In order to achieve complete regression of tumors, CSCs have to be targeted. Recent advances in immunotherapies have shown promising outcomes in curing cancer, which are also applicable to target CSCs. CSCs express immune markers and exhibit specific immune characteristics in various cancers, which can be used in immunotherapies to target CSCs in the tumor microenvironment. Recently, various strategies have been used to target CSCs. Adaptive T-cells, dendritic cell (DC)-based vaccines, oncolytic viruses, immune checkpoint inhibitors, and combination therapies are now being used to target CSCs. Here, we discuss the feasibility of these immunological approaches and the recent trends in immunotherapies to target CSCs.

Hepatocellular carcinoma is highly refractory cancer which is resistant to conventional chemotherapy and radiotherapy, carrying a dismal prognosis. Although many anticancer drugs have been developed for treating HCC, sorafenib is the only effective treatment, but it only prolongs survival duration for about 3 months. Recently, oncolytic virotherapy has shown promising results in treating HCCs and the effects can be more enhanced by adopting immune modulatory molecules. This review discusses the current status of treating HCC and the effective strategy of oncolytic virus-based immunotherapy for the treatment of HCCs.

Oncolytic virotherapy, a type of nanomedicine in which oncolytic viruses (OVs) are used to selectively infect and lyse cancer cells, is an emerging field in cancer therapy. Some OVs exhibit a specific tropism for cancer cells, whereas others require genetic modification to enhance their binding with and entry into cancer cells. OVs both kill tumor cells and induce the host’s immune response against tumor cells. Armed with antitumor cellular molecules, antibodies, and/or in combination with anticancer drugs, OVs can accelerate the lysis of cancer cells. Among the OVs, vaccinia virus has been the focus of preclinical and clinical research because of its many favorable properties. In this review, the basic mechanisms of action of OVs are presented, including their entry, survival, tumor lysis, and immune activation, and the latest research in vaccinia virus-based virotherapy and its status as an anticancer nanomedicine in prospective clinical trials are discussed.

Peritoneal metastasis, also known as peritoneal carcinomatosis (PC), is a refractory cancer that is typically resistant to conventional therapies. The typical treatment for PC is a combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Recently, research in this area has seen significant advances, particularly in immunotherapy as an alternative therapy for PC, which is very encouraging. Catumaxomab is a trifunctional antibody intraperitoneal (IP) immunotherapy authorized in Europe that can be used to diminish malignant ascites by targeting EpCAM. Intraperitoneal (IP) immunotherapy breaks immunological tolerance to treat peritoneal illness. Increasing T-cell responses and vaccination against tumor-associated antigens are two methods of treatment. CAR-T cells, vaccine-based therapeutics, dendritic cells (DCs) in combination with pro-inflammatory cytokines and NKs, adoptive cell transfer, and immune checkpoint inhibitors are promising treatments for PC. Carcinoembryonic antigen-expressing tumors are suppressed by IP administration of CAR-T cells. This reaction was strengthened by anti-PD-L1 or anti-Gr1. When paired with CD137 co-stimulatory signaling, CAR-T cells for folate receptor cancers made it easier for T-cell tumors to find their way to and stay alive in the body.