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The Role of Natural Killer Cells as a Platform for Immunotherapy in Pediatric Cancers.

Purpose of reviewWe aim to review the most recent findings in the use of NK cells in childhood cancers.Recent findingsNatural killer cells are cytotoxic to tumor cells. In pediatric leukemias, adoptive transfer of NK cells can bridge children not in remission to transplant. Interleukins (IL2, IL15) can enhance NK cell function. NK cell-CAR therapy has advantages of shorter life span that lessens chronic toxicities, lower risk of graft versus host disease when using allogeneic cells, ability of NK cells to recognize tumor cells that have downregulated MHC to escape T cells, and possibly less li

Transplant oncology and anti-cancer immunosuppressants.

Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy is required to prevent allogeneic graft rejection, which inadvertently elevates the risk of post-transplant malignancies, especially for liver transplant recipients with a prior history of liver cancer. In response, the emerging field of transplant oncology integrates principles from oncology and immunology to improve outcomes for patients at high risk of tumor occurrence or recurrence following transplantation. Therefore,

Plant-Derived Natural Products in Cancer Research: Extraction, Mechanism of Action, and Drug Formulation.

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basi

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… Treatment of MCF-7 and MDA-MB-231 breast cancer cell lines with quercetin enhances apoptosis along with G1 phase arrest [ 280 , 281 ]. … Additionally, Liu et al. reported that AKBA treated cancer cells exhibited cell arrest at G1 phase through downregulation of G1 phase cyclins and cyclin-dependent kinases (CDK). They also found that the G1 phase arrest induced by AKBA was dependent upon the expression of CDK inhibitor p21 [ 378 ]. …

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

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… Tamoxifen decreases the expression of cyclin D1 and increases the expression of p21, leading to cell cycle arrest in the G1 phase. It interferes with the signaling pathways of growth factors such as EGFR and IGF-1, which are involved in cell proliferation and survival [ 104 ]. … This modulation of gene expression facilitates the arrest of cancer cells in the G0/G1 phase of the cell cycle and promotes apoptotic cell death, reducing the growth of estrogen-dependent breast cancer cells. …

Abstracts 12th PCNE working conference 'Partnering for better patient outcomes: challenges and opportunities 3-6 February 2021, University of Basel, Switzerland (was held online).

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A Comparison of the Efficacy and Safety of Denosumab and Zoledronic Acid in Patients with Bone Metastatic Breast Cancer Receiving CDK4/6 Inhibitor Therapy.

Background and Objectives: Bone metastases in patients can cause significant quality-of-life declines due to skeletal-related events (SREs). SRE is defined as the occurrence of radiotherapy for bone pain, pathologic fracture, bone surgery, spinal cord compression, or hypercalcemia. Bone-modifying agents (BMAs), such as denosumab and zoledronic acid, are crucial in reducing the frequency and severity of SREs. The inhibition of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has emerged as the standard treatment for hormone receptor-positive metastatic breast cancer, demonstrating significant im

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review.

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells' sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene rever

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… β-Elemene has a certain effect on the cell cycle of T24 and 5637 cells, where it decreases the percentage of cells in the S phase and induces G1 phase arrest in a dose-dependent manner. … The combined treatment of β-elemene (125 g/mL) and cetuximab (25 g/mL) in KRAS mutant CRC cells HCT116 and Lovo showed a significant reduction in the activity of CRC cells, cell cycle arrest in the G0/G1 phase, and anti-proliferative effects. …

A Novel Hydroxamic Acid-Based Curcumin Derivative as Potent Histone Deacetylase Inhibitor for the Treatment of Glioblastoma.

Glioblastoma (GBM) is one of the most common primary and deadliest malignant brain tumor with chemoresistance and poor prognosis. There is a lack of effective chemotherapeutic drug for the treatment of GBM. In this work, we reported the preparation of a histone deacetylase (HDAC) inhibitor, DMC-HA, from the structural modification of natural product curcumin. DMC-HAs were tested in an HDAC inhibition assay and an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cytotoxicity. It showed potent inhibition of HDAC1-2 and HDAC6 with IC50 values in the submicromolar conce

Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma.

We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signalin

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… Inhibition of mTOR, a well-known regulator of cell cycle progression and cell proliferation, causes strong G1-phase cell cycle arrest. In addition, mTOR activity can regulate apoptotic cell death in some situations [ 233 ]. … Chen et al. have demonstrated that the combination with baicalein and silymarin in human hepatoma HepG2 cells synergistically increased the percentage of cells in G0/G1 phase and decreased those in S-phase. …

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An

Targeting the proteasome in cancer therapy: development and future opportunities in natural products.

BACKGROUND: The ubiquitin-proteasome pathway is a critical therapeutic target in malignancies, particularly multiple myeloma. The development of proteasome inhibitors (PIs) has marked a milestone in multiple myeloma therapy and now constitutes the backbone of frontline treatment regimens. However, primary and acquired resistance remain a major challenge, underscoring the need to identify new PIs as well as agents that can resensitize resistant cells. METHOD: This review provides an overview of the current clinical applications of PIs and offers a comprehensive summary of natural products that

Gene Therapy for Pancreatic Diseases: Current Status.

The pancreas is a key organ involved in digestion and endocrine functions in the body. The major diseases of the pancreas include pancreatitis, pancreatic cancer, cystic diseases, pancreatic divisum, islet cell tumors, endocrine tumors, diabetes mellitus, and pancreatic pain induced by these diseases. While various therapeutic methodologies have been established to date, however, the improvement of conventional treatments and establishment of novel therapies are essential to improve the efficacy. For example, conventional therapeutic options, including chemotherapy, are not effective against p

Targeting Autophagy Using Long Non-Coding RNAs (LncRNAs): New Landscapes in the Arena of Cancer Therapeutics.

Cancer has become a global health hazard accounting for 10 million deaths in the year 2020. Although different treatment approaches have increased patient overall survival, treatment for advanced stages still suffers from poor clinical outcomes. The ever-increasing prevalence of cancer has led to a reanalysis of cellular and molecular events in the hope to identify and develop a cure for this multigenic disease. Autophagy, an evolutionary conserved catabolic process, eliminates protein aggregates and damaged organelles to maintain cellular homeostasis. Accumulating evidence has implicated the

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… Cellular dormancy refers to a halt in the proliferative abilities of the cells, where they enter into a quiescent-like state and rest in the G0–G1 phase of the cell cycle. … Moreover, SNHG6 silencing decreased proliferation, migration, and autophagy and induced G0/G1 phase arrest and apoptosis in osteosarcoma [ 191 ]. …

A Comprehensive Single Institutional Review of 2 Years in a Designated Fast-Track Sarcoma Diagnostic Clinic Linked with a Sarcoma Specialist Advisory Group: Meeting the Target but Failing the Task?

Background. National guidelines prompted the implementation of a designated two-week wait referral pathway to facilitate the early diagnosis of sarcomas, to improve treatment outcomes. Methods. Patients referred to the Cambridge Sarcoma Diagnostic Clinic between January 2013 and December 2014 were identified through the electronic appointments system. Information was retrospectively retrieved about patient characteristics and details of the diagnostic pathway. Results. 17.3% of patients referred (69/397) were diagnosed with a malignancy. Of these, 59.3% (41/69) had primary sarcomas, 17.4% (12/

Docosahexaenoic Acid Modulates a HER2-Associated Lipogenic Phenotype, Induces Apoptosis, and Increases Trastuzumab Action in HER2-Overexpressing Breast Carcinoma Cells.

In breast cancer, lipid metabolic alterations have been recognized as potential oncogenic stimuli that may promote malignancy. To investigate whether the oncogenic nature of lipogenesis closely depends on the overexpression of HER2 protooncogene, the normal breast cell line, HB4a, was transfected with HER2 cDNA to obtain HER2-overexpressing HB4aC5.2 cells. Both cell lines were treated with trastuzumab and docosahexaenoic acid. HER2 overexpression was accompanied by an increase in the expression of lipogenic genes involved in uptake (CD36), transport (FABP4), and storage (DGAT) of exogenous fat

Immunotherapy for Cutaneous Squamous Cell Carcinoma: Results and Perspectives.

Although initial surgical excision cures 95% of patients, a minority of cutaneous squamous cell carcinomas (cSCCs) are judged to be unresectable, either locally advanced or with unresectable regional lymph nodes or distant metastases. These patients are offered systemic treatments. Response rate to chemotherapy is relatively low and not durable, as well as the results obtained with epidermal growth factor inhibitors (EGFRi). Like other cutaneous tumors, cSCCs have high immunogenicity, driven by the high mutational burden, the ultraviolet signature, and the overexpressed tumor antigens. Two che

Recent advancement in the anticancer efficacy of the natural flavonoid scutellarin: a comprehensive review.

Scutellarin (SC), a natural flavonoid, has been expansively employed in treating innumerable inflammation-related diseases due to its antitumor, antiinflammatory, anticancer, and antioxidant potential. Scutellarin can inhibit significant inflammatory cell signaling pathways, comprisingPI3K/Akt, NF-κB, and MAPK, and while activating antioxidant-related pathways such as Nrf2 and ARE. Numerous reviews have outlined scutellarin's pharmacological effects and associated mechanisms in inflammation-related diseases. Several studies have elucidated the mechanisms of anticancer activity by inhibiting va

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… SC significantly induced cell cycle arrest (G0/G1 phase) and apoptosis and in RCC (at 30, 60, and 90 μM dosage) cells. … In another study, SC significantly inhibited the growth of A549 carcinoma cells, induced substantial G0/G1 phase arrest, enhanced apoptosis and caspase activation. …

Emerging and underexplored ginsenosides in cancer therapy (2020-2025): Beyond cytotoxic mechanisms.

Ginsenosides from Panax plants have long been studied as potential anticancer agents. In earlier years, most research focused on a few well-known ginsenosides that showed strong direct cytotoxicity, such as Rg3 and Rh2. As a result, many other ginsenosides were considered less active and received limited attention. However, studies published between 2020 and 2025 indicate that several previously underexplored ginsenosides also exhibit meaningful anticancer activity. These compounds often do not function as strongly cytotoxic agents. Instead, they act through broader and more indirect mechanism

Temsirolimus in the treatment of relapsed and/or refractory mantle cell lymphoma.

Patients with mantle cell lymphoma (MCL) have a poor prognosis; consequently, new therapeutic approaches, such as rapamycin and its derivates, mammalian target of rapamycin (mTOR) inhibitors, are warranted. Temsirolimus (also known as CCI-779), a dihydroester of rapamycin, in MCL cell lines inhibited mTOR, downregulated p21 and v-Raf, and induced autophagy. The first clinical trial in MCL patients was performed using 250 mg of temsirolimus weekly for 6-12 cycles. The overall response rate was 38%; the median time to progression was 6.5 months, median overall survival was 12 months, and the med

Novel Indications for Bruton's Tyrosine Kinase Inhibitors, beyond Hematological Malignancies.

Bruton's tyrosine kinase (BTK) is a critical terminal enzyme in the B-cell antigen receptor (BCR) pathway. BTK activation has been implicated in the pathogenesis of certain B-cell malignancies. Targeting this pathway has emerged as a novel target in B-cell malignancies, of which ibrutinib is the first-in-class agent. A few other BTK inhibitors (BTKi) are also under development (e.g., acalabrutinib). While the predominant action of BTKi is the blockade of B-cell receptor pathway within malignant B-cells, increasing the knowledge of off-target effects as well as a potential role for B-cells in p

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… Ibrutinib was shown to arrest cell lines in a G0/G1 phase as well as induce apoptosis [ 25 ]. A more recent study confirmed that ibrutinib inhibits mutant EGFR kinases through formation of a covalent bond with Cys797 similar to other irreversible EGFR TKIs such as gefitinib and erlotinib [ 27 ]. …