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Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.

Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against panc

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… pathways, demonstrating good therapeutic potential.2–4 In this context, a series of drugs derived from natural products have been successfully developed and applied in clinical practice, such as paclitaxel extracted from Taxus chinensis,5 vincristine from Changchun flowers,6 and topotecan derived from camptothecin …

ER-mitochondria tethering and its signaling: A novel therapeutic target in breast cancer.

Communication between the endoplasmic reticulum (ER) and mitochondria through mitochondria-associated ER membranes (MAMs) is assisted by tethering proteins and signaling pathways, manifesting the dynamic exchange of lipids, calcium, and signaling molecules. However, dysregulation of tethering and signaling proteins contributes to the progression of breast cancer (BC). Abnormal MAM structures and altered ER-mitochondrial tethering impair mitochondrial functions and thereby drive BC progression. Altered mitochondrial dynamics, often characterized by dysregulated dynamin-related protein 1 (Drp1)

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… Overexpression of Mfn2 also sensitizes MCF-7 cells to camptothecin. 59 Purohit et al. reported that miR-195 negatively modulates mitochondrial fusion in BC cells by binding to the UTR region of Mfn2 ( Figure 2 D). 60 The fusion mechanism of mitochondria is negatively regulated by mitochondrial fission …

Beyond Formulation: Contributions of Nanotechnology for Translation of Anticancer Natural Products into New Drugs.

Nature is the largest pharmacy in the world. Doxorubicin (DOX) and paclitaxel (PTX) are two examples of natural-product-derived drugs employed as first-line treatment of various cancer types due to their broad mechanisms of action. These drugs are marketed as conventional and nanotechnology-based formulations, which is quite curious since the research and development (R&D) course of nanoformulations are even more expensive and prone to failure than the conventional ones. Nonetheless, nanosystems are cost-effective and represent both novel and safer dosage forms with fewer side effects due to m

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… It contains irinotecan, a semisynthetic analog of the natural alkaloid camptothecin, isolated from the stem bark of Camptotheca acuminata , which acts by stabilizing the complex formed by topoisomerase I and DNA, subsequently leading to DNA strand breaks and inhibition of cellular replication. …

What Drives Innovation: The Canadian Touch on Liposomal Therapeutics.

Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40⁻50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patient

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… The product generated using this technology was focused on the camptothecins (irinotecan and topotecan) [ 54 , 74 , 75 ] and one of the resulting products, Irinophore C, was more active than any other previously described irionotecan formulations. …

Galectin Targeted Therapy in Oncology: Current Knowledge and Perspectives.

The incidence and mortality of cancer have increased over the past decades. Significant progress has been made in understanding the underpinnings of this disease and developing therapies. Despite this, cancer still remains a major therapeutic challenge. Current therapeutic research has targeted several aspects of the disease such as cancer development, growth, angiogenesis and metastases. Many molecular and cellular mechanisms remain unknown and current therapies have so far failed to meet their intended potential. Recent studies show that glycans, especially oligosaccharide chains, may play a

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… In two other reports, however, low levels of Gal-4 were associated with an advanced form of colorectal cancer [ 116 , 117 ], while stimulation of Gal-4 expression caused colorectal cancer cells to become sensitized to Camptothecin [ 117 ]. …

Comprehensive machine learning analysis of PANoptosis signatures in multiple myeloma identifies prognostic and immunotherapy biomarkers.

PANoptosis is closely associated with tumorigenesis and therapeutic response, yet its role in multiple myeloma (MM) remains unclear. This study analyzed bulk transcriptomic and clinical data from the TCGA and GEO databases to identify seven PANoptosis-related genes (PRGs) using machine learning (LASSO regression and random forest models) and univariate Cox analysis, and constructed a prognostic risk model. The model demonstrated robust predictive performance across three external validation cohorts. High-risk patients exhibited higher tumor purity, increased tumor mutational burden, and distin

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… Synergism of AZD6738, an ATR inhibitor, in combination with belotecan, a camptothecin analogue, in Chemotherapy-Resistant ovarian Cancer. Int. J. Mol. Sci. 22 10.3390/ijms22031223 (2021). 10.3390/ijms22031223 PMC7865398 33513721 33. …

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy.

Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating

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… Vincristine and Vinblastine (vinca alkaloids extracted from Catharanthus roseus and Apocynaceae ), Paclitaxel (diterpenoid compound derived from Taxus brevifolia ), Etoposide (semisynthetic podophyllotoxin extracted from Podophyllum peltatum ), and Camptothecin (alkaloid derived from Camptotheca acuminata …

The promising role of antibody drug conjugate in cancer therapy: Combining targeting ability with cytotoxicity effectively.

IntroductionTraditional cancer therapy has many disadvantages such as low selectivity and high toxicity of chemotherapy, as well as insufficient efficacy of targeted therapy. To enhance the cytotoxic effect and targeting ability, while reducing the toxicity of antitumor drugs, an antibody drug conjugate (ADC) was developed to deliver small molecular cytotoxic payloads directly to tumor cells by binding to specific antibodies via linkers.MethodBy reviewing published literature and the current progress of ADCs, we aimed to summarize the basic characteristics, clinical progress, and challenges of

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… differentiation; CTCL, cutaneous T‐cell lymphoma; DLBCL, diffuse large B‐cell lymphoma; DM1, maytansinoids; HL, Hodgkin lymphoma; IgG, immunoglobulin G; MM, multiple myeloma; MMAE, monomethyl auristatin E; MMAF, monomethyl auristatin F; NHL, non‐Hodgkin lymphoma; PTCL, peripheral T‐cell lymphoma; SN‐38, camptothecin …

Efficacy of Polymer-Based Nanocarriers for Co-Delivery of Curcumin and Selected Anticancer Drugs.

Cancer remains a heavy health burden resulting in a high rate of mortality around the world. The presently used anticancer drugs suffer from several shortcomings, such as drug toxicity, poor biodegradability and bioavailability, and poor water solubility and drug resistance. Cancer is treated effectively by combination therapy whereby two or more anticancer drugs are employed. Most of the combination chemotherapies result in a synergistic effect and overcome drug resistance. Furthermore, the design of polymer-based nanocarriers for combination therapy has been reported by several researchers t

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… Examples anticancer drugs ( Figure 2 ) that have been combined with curcumin are doxorubicin 4 , camptothecin 5 , 5-fluorouracil 6 , methotrexate 7 , paclitaxel 8 , docetaxel 9 , oxaliplatin 10 , cisplatin 11 , carboplatin 12 , melphalan 13 and cyclophosphamide 14. …

Advances in nanotechnology-enabled adjuvants for peptide-based cancer vaccines.

Peptide-based vaccines only contain peptide epitopes and exclude unnecessary biological materials, which greatly reduces the risk of causing an undesired immune response and further improves the safety profile, garnering considerable interest in vaccine development. However, the immunogenicity induced by these peptides alone is not potent enough to elicit an effective immune response. Recently, combining the adjuvants with peptide antigens has shown promising effects to realize a satisfying immune response. In this review, we discuss the development of immunoadjuvants to enhance the safety and

HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies.

The hypoxic microenvironment is an essential characteristic of most malignant tumors. Notably, hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulatory factor of cellular adaptation to hypoxia, and many critical pathways are correlated with the biological activity of organisms via HIF-1α. In the intra-tumoral hypoxic environment, HIF-1α is highly expressed and contributes to the malignant progression of tumors, which in turn results in a poor prognosis in patients. Recently, it has been indicated that HIF-1α involves in various critical processes of life events and tumor development via r

Drug-Drug Interactions of Cannabidiol with Standard-of-Care Chemotherapeutics.

Cannabidiol (CBD) is an easily accessible and affordable Marijuana (Cannabis sativa L.) plant derivative with an extensive history of medical use spanning thousands of years. Interest in the therapeutic potential of CBD has increased in recent years, including its anti-tumour properties in various cancer models. In addition to the direct anticancer effects of CBD, preclinical research on numerous cannabinoids, including CBD, has highlighted their potential use in: (i) attenuating chemotherapy-induced adverse effects and (ii) enhancing the efficacy of some anticancer drugs. Therefore, CBD is ga

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… The Mechanism of Topoisomerase I Poisoning by a Camptothecin Analog. Proc. Natl. Acad. Sci. USA. 2002;99:15387–15392. doi: 10.1073/pnas.242259599. 130. Devriese L.A., Witteveen P.E.O., Mergui-Roelvink M., Smith D.A., Lewis L.D., Mendelson D.S., Bang Y. …

Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.

The nervous system plays a critical role in developmental biology and oncology, influencing processes from ontogeny to the complex dynamics of cancer progression. Interactions between the nervous system and cancer significantly affect oncogenesis, tumor growth, invasion, metastasis, treatment resistance, inflammation that promotes tumors, and the immune response. A comprehensive understanding of the signal transduction pathways involved in cancer biology is essential for devising effective anti-cancer strategies and overcoming resistance to existing therapies. Recent advances in cancer neurosc

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… Simultaneous treatment with camptothecin and valproic acid suppresses induction of Bcl-X(L) and promotes apoptosis of MCF-7 breast cancer cells. Apoptosis. 2009;14:1076–85. 10.1007/s10495-009-0384-0. 106. Kabakus N, et al. …

Repositioning of drugs for Parkinson's disease and pharmaceutical nanotechnology tools for their optimization.

Parkinson's disease (PD) significantly affects patients' quality of life and represents a high economic burden for health systems. Given the lack of safe and effective treatments for PD, drug repositioning seeks to offer new medication alternatives, reducing research time and costs compared to the traditional drug development strategy. This review aimed to collect evidence of drugs proposed as candidates to be reused in PD and identify those with the potential to be reformulated into nanocarriers to optimize future repositioning trials. We conducted a detailed search in PubMed, Web of Science,

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… In this context, Shen et al. developed linear conjugates of polymer-drug by conjugating one or two molecules of strong hydrophobic camptothecin (CPT) to a very short oligoethylene glycol chain, reaching a drug load content of 40 to 58% [ 103 ]. …

Systematic literature review of IL-6 as a biomarker or treatment target in patients with gastric, bile duct, pancreatic and colorectal cancer.

Gastrointestinal cancer (GI) is a major health problem. Patients with gastric, pancreatic, colorectal, bile duct and gall bladder cancer often have advanced disease at the time of diagnosis and are generally difficult to cure, resulting in a dismal prognosis for most patients. Inflammation plays an important role in the development and growth of cancer, which has led to a growing interest in the pro-inflammatory cytokine interleukin 6 (IL-6). The aim of the present review was to evaluate the clinical use of IL-6 as a biomarker or therapeutic target in patients with GI cancer. We did a systemat

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… RKIP phosphorylation and STAT3 activation is inhibited by oxaliplatin and camptothecin and are associated with poor prognosis in stage II colon cancer patients. BMC Cancer. 2013;13:463. doi: 10.1186/1471-2407-13-463. 14. Zhou B, Shu B, Yang J, Liu J, Xi T, Xing Y. …

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed b

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… Wyatt and Davis compared the uptake and antitumor efficacies of transferrin receptor (TfR)-targeted, camptothecin-conjugated polymeric nanoparticles in three BC brain metastasis models [ 107 ]. …

Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy.

Cancer therapies have advanced tremendously throughout the last decade, yet multiple factors still hinder the success of the different cancer therapeutics. The traditional therapeutic approach has been proven insufficient and lacking in the suppression of tumor growth. The simultaneous delivery of multiple small-molecule chemotherapeutic drugs and genes improves the effectiveness of each treatment, thus optimizing efficacy and improving synergistic effects. Nanomedicines integrating inorganic, lipid, and polymeric-based nanoparticles have been designed to regulate the spatiotemporal release of

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… Another study experimented with a graft copolymer with side drug segments that form nanostructures utilizing a protein folding route to distribute camptothecin (CPT) and doxorubicin [ 19 , 125 ]. The assembly of this nanoparticle is driven by the hydrophobicity of the conjugated CPT. …

Revisiting strategies to target ABC transporter-mediated drug resistance in CNS cancer.

A significant number of anticancer drugs fail to treat primary and metastatic brain tumors primarily because of the complex blood-brain barrier (BBB) and overexpression of ATP-binding cassette (ABC) transporters, which decrease drug penetration into the central nervous system and ultimately into tumors. It is noteworthy that the ABC transporters, ABCB1 [known as P-glycoprotein (P-gp)] and ABCG2 [known as breast cancer resistance protein (BCRP)], are overexpressed in brain tumors, including common gliomas. The co-presence of these transporters may negate the inhibition of either transporter, pa

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… reductase inhibitor: methotrexate (MTX) ATP Binding Cassette Subfamily C Member 1 (ABCC1) 24 – 26 | Multidrug resistance-associated protein 1 (MRP1) | Anionic lipophilic overlap specificity with ABCB1 and ABCG2 | Alkylating agents: cyclophosphamide Topoisomerase inhibitors: doxorubicin, etoposide, camptothecin …

Effects of Carbon Nanomaterials and Aloe vera on Melanomas-Where Are We? Recent Updates.

Melanoma is an aggressive skin cancer that affects approximately 140,000 people worldwide each year, with a high fatality rate. Available treatment modalities show limited efficacy in more severe cases. Hence, the search for new treatment modalities, including immunotherapies, for curing, mitigating, and/or preventing cancer is important and urgently needed. Carbon nanoparticles associated with some plant materials, such as Aloe vera, have shown appealing antineoplastic activity, derived mainly from the compounds aloin, aloe-emodin, barbaloin acemannan, and octapeptide, thus representing new p

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… Sahoo et al. have functionalized MWCNTs and GO with the anticancer therapeutic drug camptothecin (CPT), and the resulting DDS was highly biocompatible and hydrophilic [ 110 ]. …

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their m

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… rash, mucositis, febrile neutropenia, and decreased appetite CD79β | Polatuzumab; vedotin-piiq; Polivy® | Auristatin | DLBLC | IRR, neutropenia, thrombocytopenia, anemia, peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, pneumonia CCR4 | Sacituzumab govitecan-hziy; Trodelvy® | Camptothecin …