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Latest advances in extracellular vesicles: from bench to bedside.

Extracellular vesicles (EVs) are small membraned vesicles and approximately 50-150 nm in diameter. Almost all of the type of cells releases the EVs and circulates in the body fluids. EVs contain multiple functional components, such as mRNAs, microRNAs (miRNAs), DNAs, and proteins, which can be transferred to the recipient cells, resulting in phenotypic changes. Recently, EV research has focused on their potential as a drug delivery vehicle and in targeted therapy against specific molecules. Moreover, some surface proteins are specific to particular diseases, and therefore, EVs also have promis

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… Genome Med . 2018 ; 10 : 23 . 29580275 10.1186/s13073-018-0535-4 PMC5868069 [110] Kitai Y , Kawasaki T , Sueyoshi T , et al DNA-containing exosomes derived from cancer cells treated with topotecan activate a STING-dependent pathway and reinforce antitumor immunity . …

Treatment of multiple myeloma with selinexor: a review.

Over the last 20 years, breakthroughs in accessible therapies for the treatment of multiple myeloma (MM) have been made. Nevertheless, patients with MM resistant to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies have a very poor outcome. Therefore, it is necessary to explore new drugs for the treatment of MM. This review summarizes the mechanism of action of selinexor, relevant primary clinical trials, and recent developments in both patients with relapsed/refractory myeloma and patients with newly diagnosed myeloma. Selinexor may be useful for the treatment

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… Similar to selinexor, eltanexor also produces synergistic effects with dexamethasone. 87 Eltanexor acted synergistically with common anti-MM drugs, including bortezomib, carfilzomib, doxorubicin, melphalan, topotecan, and etoposide and induced apoptosis in numerous MM cell lines, as shown by Turner et …

Targeting BCL-XL in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare and often lethal liver cancer with no proven effective systemic therapy. Inhibition of the antiapoptotic protein BCL-XL was found to synergize with a variety of systemic therapies in vitro using cells dissociated from patient-derived xenografts (PDX) of FLC or cells dissociated directly from surgical patient resections. As BCL-XL is physiologically expressed in platelets, prior efforts to leverage this vulnerability in other cancers have been hampered by severe thrombocytopenia. To overcome this toxicity, we treated FLC models with DT2216,

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… Efficacy of topoisomerase I inhibitors, topotecan and irinotecan, administered at low dose levels in protracted schedules to mice bearing xenografts of human tumors. Cancer Chemother Pharmacol. 1995;36(5):393–403. doi: 10.1007/BF00686188. 29. Oguri T, et al. …

Artificial intelligence in drug discovery and development.

Artificial intelligence-integrated drug discovery and development has accelerated the growth of the pharmaceutical sector, leading to a revolutionary change in the pharma industry. Here, we discuss areas of integration, tools, and techniques utilized in enforcing AI, ongoing challenges, and ways to overcome them.

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… Cellular network-based deep learning technology (deepDTnet) has been explored to predict the therapeutic use of topotecan, currently used as a topoisomerase inhibitor. …

Valproic acid potentiates the anticancer activity of capecitabine in vitro and in vivo in breast cancer models via induction of thymidine phosphorylase expression.

The prognosis of patients with metastatic breast cancer remains poor, and thus novel therapeutic approaches are needed. Capecitabine, which is commonly used for metastatic breast cancer in different settings, is an inactive prodrug that takes advantage of elevated levels of thymidine phosphorylase (TP), a key enzyme that is required for its conversion to 5-fluororacil, in tumors. We demonstrated that histone deacetylase inhibitors (HDACi), including low anticonvulsant dosage of VPA, induced the dose- and time-dependent up-regulation of TP transcript and protein expression in breast cancer cell

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… expression by HDAC inhibitor vorinostat resulted in synergistic antitumor effect in combination with 5FU or raltitrexed Cancer Biol Ther 2009 8 782 791 19270508 10.4161/cbt.8.9.8118 17 Bruzzese F Rocco M Castelli S Di Gennaro E Desideri A Budillon A Synergistic antitumor effect between vorinostat and topotecan …

Looking for the Holy Grail-Drug Candidates for Glioblastoma Multiforme Chemotherapy.

Glioblastoma multiforme (GBM) is the deadliest and the most heterogeneous brain cancer. The median survival time of GBM patients is approximately 8 to 15 months after initial diagnosis. GBM development is determined by numerous signaling pathways and is considered one of the most challenging and complicated-to-treat cancer types. Standard GBM therapy consist of surgery followed by radiotherapy or chemotherapy, and combined treatment. Current standard of care (SOC) does not offer a significant chance for GBM patients to combat cancer, and the selection of available drugs is limited. For almost

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… It was confirmed that AR-67 is characterized by improved safety and lipophilicity compared to current drugs in this class, such as Topotecan and Irinotecan [ 84 ]. A phase 1 clinical trial of AR-67 was conducted on cancer patients with solid tumors. …

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature.

Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In

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… they were receiving chemotherapy with 5-FU. 114 Gemcitabine may occasionally evoke peripheral neuropathy with paresthesias and myalgias, whereas neurotoxicity rarely occurs while patients are treated with methotrexate, cytosine arabinoside (Ara-C), or topoisomerase inhibitors, such as irinotecan or topotecan …

Dermatologic conditions in women receiving systemic cancer therapy.

As advances in cancer therapies have improved cancer-related survival, novel therapeutics have also introduced a variety of dermatologic toxicities, and an increased number of patients are living with these sequalae. Women with cancer in particular experience a spectrum of dermatologic conditions that affect their skin, hair, nail, and mucosal surfaces. Studies have shown that these toxic effects can significantly affect quality of life and alter a woman's self-image, cultural identity, femininity, sexuality, and mental health. In severe instances, dermatologic toxicities may even disrupt canc

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… transplantation | Thiotepa | Breast, ovarian, bladder, Hodgkin’s disease Platinum-based | Cisplatin | Testicular, ovarian, breast, cervical, bladder, head and neck, esophageal, lung, mesothelioma, brain, neuroblastoma | Carboplatin | Ovarian, lung | Oxaliplatin | Colorectal Topoisomerase inhibitors | Topotecan … Some of the most common causative agents include PLD, bleomycin, dactinomycin, docetaxel, doxorubicin, 5-FU, methotrexate (MTX), and topotecan ( Susser et al., 1999 ). …

Role of PARP Inhibitors in Cancer Immunotherapy: Potential Friends to Immune Activating Molecules and Foes to Immune Checkpoints.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxic effects as single agents in tumors characterized by defective repair of DNA double-strand breaks deriving from BRCA1/2 mutations or other abnormalities in genes associated with homologous recombination. Preclinical studies have shown that PARPi-induced DNA damage may affect the tumor immune microenvironment and immune-mediated anti-tumor response through several mechanisms. In particular, increased DNA damage has been shown to induce the activation of type I interferon pathway and up-regulation of PD-L1 expression in cance

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… with recurrent or progressing endometrial or ovarian cancer, following at least a first line of platinum-based chemotherapy, are being randomized to receive either niraparib as monotherapy or niraparib in combination with dostarlimab or standard chemotherapy (paclitaxel, doxorubicine, gemcitabine, and topotecan …

Early Experience with Tarlatamab (T-Cell Engagers) for Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Canada: Lessons Learned and Implementation Strategies.

As bispecific T-cell engagers (TCEs) gain traction in the oncology treatment landscape, cancer centres must develop robust clinical pathways to ensure their safe and efficient delivery. Given the limited experience of the Canadian medical oncology community with TCEs, collecting and publishing early clinical experiences with these novel agents will be essential to inform best practices and support their safe and effective adoption across the broader Canadian oncology community. The approval of tarlatamab, the first-in-class delta-like ligand 3 (DLL3)-targeted TCE for extensive-stage small cell

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… In this study, patients receiving tarlatamab (n = 254) are compared with those receiving standard chemotherapy (topotecan, lurbinectedin, or amrubicin; n = 255). The primary endpoint is OS, with secondary endpoints including ORR, DCR, and duration of DOR. …

Pharmacogenomics and Big Data in medical oncology: developments and challenges.

Medical oncology, through conventional chemotherapy as well as targeted drugs, remains an important component of cancer patient management, particularly for systemic disease. Despite advances in all areas of medical oncology, certain challenges persist in the form of drug resistance and severe normal tissue toxicity. These unwanted effects can be counteracted through a patient-tailored treatment approach, which in chemotherapy is translated as pharmacogenomics. This research field investigates the way genetic makeup influences a patient's response to various drugs with the aim to minimize tria

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… damage | Wide-ranging cancers | 8 , 9 Nitrosoureas (similar to alkylating agents) | Carmustine, Lomustine Semustin, Streptozocin | Inhibit DNA repair; they can cross the blood–brain barrier thus are useful for brain tumours | Brain | 10 , 11 Topoisomerase inhibitors (plant alkaloids) | Irinotecan, Topotecan …

Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.

Currently, chemotherapy is the main treatment for tumors, but there are still problems such as unsatisfactory chemotherapy results, susceptibility to drug resistance, and serious adverse effects. Natural compounds have numerous pharmacological activities which are important sources of drug discovery for tumor treatment. The combination of chemotherapeutic drugs and natural compounds is gradually becoming an important strategy and development direction for tumor treatment. In this paper, we described the role of natural compounds in combination with chemotherapeutic drugs in synergizing, reduci

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… MHP-1 inhibits cancer metastasis and restores topotecan sensitivity via regulating epithelial-mesenchymal transition and TGF-β signaling in human breast cancer cells Phytomed. Int. J. Phytother. Phytopharm. 2016 23 1053 1063 10.1016/j.phymed.2016.06.013 27444351 100. Cropper J.D. Alimbetov D.S. …

Regulation of microRNAs by natural agents: new strategies in cancer therapies.

MicroRNAs (miRNAs) are short noncoding RNA which regulate gene expression by messenger RNA (mRNA) degradation or translation repression. The plethora of published reports in recent years demonstrated that they play fundamental roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation by acting as tumour suppressor or oncogene, and aberrations in their expressions have been linked to onset and progression of various cancers. Furthermore, each miRNA is capable of regulating the expression of many

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… Hence, many of the anticancer agents currently used in cancer therapies have been developed from natural products such as plants (vincristine, vinblastine, etoposide, paclitaxel, camptothecin, topotecan, and irinotecan), marine organisms (cytarabine), and microorganisms (dactinomycin, bleomycin, and …

Leptomeningeal carcinomatosis in gastric cancer: A Review.

Gastric cancer is the fifth most common cancer worldwide and leptomeningeal carcinomatosis (LM) occurs in 0.06% of gastric cancers. As such, trials are difficult to power and quantitative analyses difficult to standardize. We composed a review and analysis of 47 recent cases to be used as a comprehensive resource for an oncologist faced with managing this highly morbid, rapidly fatal disease. Gold-standard of diagnosis of LM is through cerebral spinal fluid (CSF) cytology; MRI is the preferred imaging modality to identify LM. However, repeated lumbar punctures and imaging studies are often req

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… NCCN guidelines recommend systemic therapy specific to the primary cancer type and intrathecal chemotherapy with thiotepa, topotecan, etoposide, cytarabine, or methotrexate – doses and duration of treatment are not included [ 34 ]. …

The Battlefield of Chemotherapy in Pediatric Cancers.

The survival rate for pediatric cancers has remarkably improved in recent years. Conventional chemotherapy plays a crucial role in treating pediatric cancers, especially in low- and middle-income countries where access to advanced treatments may be limited. The Food and Drug Administration (FDA) approved chemotherapy drugs that can be used in children have expanded, but patients still face numerous side effects from the treatment. In addition, multidrug resistance (MDR) continues to pose a major challenge in improving the survival rates for a significant number of patients. This review focuses

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… The mouse Bcrp1/Mxr/Abcp gene: Amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res. 1999;59:4237–4241. 133. Wei G., Wang Y., Yang G., Wang Y., Ju R. Recent progress in nanomedicine for enhanced cancer chemotherapy. …

Recent Progress in CDK4/6 Inhibitors and PROTACs.

Cell division in eukaryotes is a highly regulated process that is critical to the life of a cell. Dysregulated cell proliferation, often driven by anomalies in cell Cyclin-dependent kinase (CDK) activation, is a key pathological mechanism in cancer. Recently, selective CDK4/6 inhibitors have shown clinical success, particularly in treating advanced-stage estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This review provides an in-depth analysis of the action mechanism and recent advancements in CDK4/6 inhibitors, categorizing them based

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… On 12 February 2021, trilaciclib received its first approval in the USA to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC …

An overview of antibody-drug conjugates in oncological practice.

Antibody-drug conjugates (ADCs) are designed to manipulate the toxic efficacy of specific chemotherapeutic compounds, employing the high affinity of antibody-mediated delivery so as to drive them selectively to target cancer cells. These immunoconjugates encompass the general tendency towards precision medicine and avert the systemic toxicities of conventional chemotherapy, accomplishing an improved therapeutic index. Cumulative experience acquired from first-generation ADCs offers new perspectives to these promising therapeutic modalities for various hematological and solid cancers and propel

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… NCT02665065 | R/R AML | (a) Conventional care including: GO, azacytidine, carboplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, daunorubicin, decitabine, doxorubicin, enasidenib, etoposide, fludarabine, idarubicin, ivosidenib, l-asparaginase, midostaurin, mitoxantrone, sorafenib, thioguanine, topotecan …

Molecular Targeting and Rational Chemotherapy in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a molecularly complex disease with multiple aberrant genetic pathways involved in its pathogenesis. Approximately one-third to one-half of patients with AML would relapse, and no standard therapy is established for relapsing and/or refractory AML (RR-AML) yet. It is unlikely that blockage of only one specific pathway will lead to prolonged remissions and cures in all fractions of the AML patients population. Nowadays, novel therapeutic agents with rational combination are being recognized which improve the cure rate for relapsed AML. These drugs and their metabo

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… Topoisomerase targeting causes topoisomerase-mediated DNA strand breaks. 14 Several cytotoxic Top II inhibitors are currently supplied in salvage chemotherapy for RR-AML. 1 , 4 , 5 The Top I inhibitors; irinotecan, topotecan, karenitecin and camptothecin are used for colorectal, gastric, lung and cervical …

Prophylactic Oophorectomy: Reducing the U.S. Death Rate from Epithelial Ovarian Cancer. A Continuing Debate.

If instead of the title "Prophylactic Oophorectomy: Reducing the U.S. Death Rate from Epithelial Ovarian Cancer," the title were "Drug X Reducing the U.S. Death Rate from Epithelial Ovarian Cancer," there would be great media and medical attention worldwide to such a report. Correctly so. Regrettably, there probably is no new Drug X in the foreseeable future that will significantly reduce the death rate from ovarian cancer, be it Taxol®, taxotere, topotecan, gemcitabine, or liposomal doxorubicin-although each may result in significant responses and some prolongation of median survival. Epi…

Second-Generation Antimitotics in Cancer Clinical Trials.

Mitosis represents a promising target to block cancer cell proliferation. Classical antimitotics, mainly microtubule-targeting agents (MTAs), such as taxanes and vinca alkaloids, are amongst the most successful anticancer drugs. By disrupting microtubules, they activate the spindle assembly checkpoint (SAC), which induces a prolonged delay in mitosis, expected to induce cell death. However, resistance, toxicity, and slippage limit the MTA's effectiveness. With the desire to overcome some of the MTA's limitations, mitotic and SAC components have attracted great interest as promising microtubule

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… relapsed or refractory hematological malignancies | [ 150 , 151 , 152 , 153 , 154 , 155 , 156 , 167 ] LY3295668 (Erbumine) | 4 Clinical trials | Phase I/II 2 Completed 1 Recruiting 1 Planned | Small-Cell Lung Cancer, Metastatic Breast Cancer, Neuroblastoma, Solid Tumors | Monotherapy Combination with Topotecan … Currently, a phase I trial is ongoing for the treatment of small-cell lung cancer ( NCT03898791 ) with LY3295668 as monotherapy, and another phase I study with LY3295668 in combination with Topotecan and Cyclophosphamide in patients with neuroblastoma is recruiting participants ( NCT04106219 ). 4.3.4 …