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Targeting mTOR and Metabolism in Cancer: Lessons and Innovations.

Cancer cells support their growth and proliferation by reprogramming their metabolism in order to gain access to nutrients. Despite the heterogeneity in genetic mutations that lead to tumorigenesis, a common alteration in tumors occurs in pathways that upregulate nutrient acquisition. A central signaling pathway that controls metabolic processes is the mTOR pathway. The elucidation of the regulation and functions of mTOR can be traced to the discovery of the natural compound, rapamycin. Studies using rapamycin have unraveled the role of mTOR in the control of cell growth and metabolism. By sen

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… Cytotoxic Chemotherapy | | Carboplatin | DNA | [ 264 , 265 , 266 ] Paclitaxel | Microtubules | [ 266 , 267 , 268 ] Cisplatin | DNA | [ 268 , 269 ] Vinorelbine | Microtubules | [ 244 , 270 ] Cyclophosphamide | DNA | [ 271 ] Doxorubicin | Topoisomerase | [ 272 ] Vincristine | Microtubules | [ 273 ] Docetaxel … In a study that used temsirolimus as maintenance therapy in castration-resistant prostate cancer after docetaxel induction, the regimen proved safe, and delayed the time to treatment failure to 6 months [ 274 ]. …

Epigenetics-targeted drugs: current paradigms and future challenges.

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifyin

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

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… expressing tumors | I/II | 2023 | NCT04143711 | 131 | SAR445514(IPH64) | Single agent | Relapsed/refractory multiple myeloma and relapsed/refractory light chain amyloidosis | I/II | 2023 | NCT05839626 | 130 TAMs | Inhibit recruitment | Carlumab/CNTO 888 (anti-CCL2 antibody) | Combined chemotherapy (docetaxel … Initially, the recruitment of TAMs was inhibited using the anti-CCL2 antibody Carlumab/CNTO 888, in combination with multiple chemotherapy drugs such as docetaxel, gemcitabine, and paclitaxel 149 . …

From laboratory to clinic: opportunities and challenges of functional food active ingredients in cancer therapy.

This review provides a comprehensive analysis of the potential of functional food active ingredients in cancer prevention and therapy. It outlines the multifaceted anticancer mechanisms of bioactive compounds-such as polyphenols, carotenoids, omega-3 fatty acids, phytosterols, alkaloids, isothiocyanates, polysaccharides, phenolic acids, flavonols, and amide-bearing compounds-which include antioxidant and anti-inflammatory activities, induction of apoptosis and autophagy, modulation of the tumor microenvironment, interference with cell cycle regulation and signaling pathways, and regulation of

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… Bcl-2 shift; thymidylate-synthase downregulation | IC 50 of 5-FU ↓≈ 8-fold in HCT-116 xenografts; tumor volume ↓ 75 % EGCG (green-tea catechin) | 5-Fluorouracil | MDR1 and MRP2 downregulation; autophagy induction | Multidrug-resistant HT-29 cells resensitized (viability ↓> 60 %) Sulforaphane (ITC) | Docetaxel … | CSC depletion (ALDH 1+ , CD44 + /α2β1 + ↓); NF-κB inhibition | DU-145 xenograft growth delay doubled vs. docetaxel alone Resveratrol (polyphenol) | Doxorubicin | Topo-IIα stabilisztion; ROS buffering → cardioprotection while promoting tumor ROS burst | MCF-7 tumors: apoptosis ↑ 2 × ; rat hearts: CK-MB …

Development of a machine learning-based predictive risk model combining fatty acid metabolism and ferroptosis for immunotherapy response and prognosis in prostate cancer.

Prostate cancer (PCa) remains a leading cause of cancer-related mortality, necessitating robust prognostic models and personalized therapeutic strategies. This study integrated bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to construct a prognostic model based on genes shared between ferroptosis and fatty acid metabolism (FAM). Using the TCGA-PRAD dataset, we identified 73 differentially expressed genes (DEGs) at the intersection of ferroptosis and FAM, of which 19 were significantly associated with progression-free survival (PFS). A machine learning-

Clinical outcomes of chemotherapy in cancer patients with different ethnicities.

BackgroundChoosing the most effective chemotherapeutic agent with safest side effect profile is a common challenge in cancer treatment. Although there are standardized chemotherapy protocols in place, protocol changes made after extensive clinical trials demonstrate significant improvement in the efficacy and tolerability of certain drugs. The pharmacokinetics, pharmacodynamics, and tolerance of anti-cancer medications are all highly individualized. A driving force behind these differences lies within a person's genetic makeup.Recent findingsPharmacogenomics, the study of how an individual's g

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… Induction chemotherapy with docetaxel, cisplatin, fluorouracil and l‐leucovorin for locally advanced head and neck cancers: a modified regimen for Japanese patients. Anticancer Drugs. 2003;14(10):801‐807. 60. Soo RA, Kawaguchi T, Loh M, et al. … Docetaxel and carboplatin is an active regimen in advanced non‐small‐cell lung cancer: a phase II study in Caucasian and Asian patients. Ann Oncol. 2003;14(3):449‐454. 72. Khrunin A, Ivanova F, Moisseev A, et al. …

Current Data and Future Perspectives on Patients with Atrial Fibrillation and Cancer

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… There is a strong temporal relationship between therapy with taxanes, such as paclitaxel and docetaxel, used for the treatment of many cancers, such as breast and lung cancer, and the development of severe skin and mucosal toxicity due to the reduced clearance of taxanes in patients taking amiodarone …

Trametinib in Patients With NF1-, GNAQ-, or GNA11-Mutant Tumors: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols S1 and S2.

PURPOSE: NCI-MATCH is a precision medicine trial using genomic testing to allocate patients with advanced malignancies to targeted treatment subprotocols. This report combines two subprotocols evaluating trametinib, a MEK1/2 inhibitor, in patients with Neurofibromatosis 1 (NF1[S1] or GNA11/Q [S2]) altered tumors. METHODS: Eligible patients had tumors with deleterious inactivating NF1 or GNA11/Q mutations by the customized Oncomine AmpliSeq panel. Prior MEK inhibitor treatment was excluded. Glioblastomas (GBMs) were permitted, including malignancies associated with germline NF1 mutations (S1 o

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… Blumenschein GR Jr Smit EF Planchard D et al A randomized phase II study of the MEK1/MEK2 inhibitor trametinib (GSK1120212) compared with docetaxel in KRAS-mutant advanced non-small-cell lung cancer (NSCLC) Ann Oncol 26 894 901 2015 25722381 10.1093/annonc/mdv072 PMC4855243 40. …

Integrated Network Pharmacology Approach for Drug Combination Discovery: A Multi-Cancer Case Study.

Despite remarkable efforts of computational and predictive pharmacology to improve therapeutic strategies for complex diseases, only in a few cases have the predictions been eventually employed in the clinics. One of the reasons behind this drawback is that current predictive approaches are based only on the integration of molecular perturbation of a certain disease with drug sensitivity signatures, neglecting intrinsic properties of the drugs. Here we integrate mechanistic and chemocentric approaches to drug repositioning by developing an innovative network pharmacology strategy. We developed

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… In BRCA, LUSC and PRAD the drug combinations are mainly composed by a drug targeting the tubulin system (such as paclitaxel, vinblastine, vincristine, docetaxel, vinorelbine) already employed in the clinical treatment of several cancers, and a drug belonging to an unusual functional category, such as …

Pre-approval and post-approval availability of evidence and clinical benefit of conditionally approved cancer drugs in Europe: A comparison with standard approved cancer drugs.

AimsCancer drugs are increasingly approved through expedited regulatory pathways including the European conditional marketing authorization (CMA). Whether, when taking CMA post-approval confirmatory trials into account, the level of evidence and clinical benefit between CMA and standard approved (SMA) drugs differs remains unknown.MethodsWe identified all CMA cancer indications converted to SMA in 2006-2020 and compared these to similar SMA indications with regard to pivotal trial and CMA post-approval confirmatory trial design, outcomes and demonstrated clinical benefit (per the European Soci

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… For gefitinib, these failed to show a difference in OS and demonstrated non‐inferiority to treatment with docetaxel, respectively. For pembrolizumab, these had planned interim analyses of the co‐primary endpoint PFS that mainly supported approval while OS data were not yet mature. …

Dermatologic Adverse Events Associated with Selective Fibroblast Growth Factor Receptor Inhibitors: Overview, Prevention, and Management Guidelines.

Fibroblast growth factor receptor (FGFR) tyrosine kinases, which are expressed on the cell membrane, are involved in a wide range of biological functions such as cell proliferation, survival, migration, and differentiation. The identification of FGFR fusions and other alterations in a wide range of solid tumors, including cholangiocarcinoma and bladder cancer, has resulted in the development of several selective FGFR inhibitors for use in these indications, for example, infigratinib, erdafitinib, derazantinib, pemigatinib, and futibatinib. In addition to the typical adverse events associated w

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… Derazantinib vs. derazantinib + atezolizumab | 303 Futibatinib (TAS‐120) NCT04024436 | II | Breast cancer | Futibatinib or futibatinib + fulvestrant | 168 NCT02052778 | I/II | Solid tumors | Futibatinib | 371 Erdafitinib (JNJ‐42756493) NCT03390504 | III | Urothelial cancer | Erdafitinib vs. vinflunine or docetaxel …

HOTTIP Predicts Poor Survival in Gastric Cancer Patients and Contributes to Cisplatin Resistance by Sponging miR-216a-5p.

Gastric cancer (GC) is a significant public health burden worldwide, and cisplatin resistance is the leading cause for the failure of chemotherapy in this disease. Previous studies have revealed that HOXA transcript at the distal tip (HOTTIP) is involved in the pathology of GC and is associated with poor overall survival. However, the functional role of HOTTIP in GC chemoresistance remains unclear. In this study, quantitative real-time PCR was used to analyze HOTTIP expression in GC cell lines and in tissues of GC patients who received cisplatin-based chemotherapy. The mechanism of HOTTIP-medi

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… A phase II study of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1, followed by gastrectomy with D2 lymph node dissection for high-risk advanced gastric cancer: results of the KDOG1001 trial. Gastr. Cancer 22 598–606. 10.1007/s10120-018-0884-0 Hu Y., Zhu Q. N., Deng J. L., Li Z. …

A recommended practical approach to the management of target therapy and angiogenesis inhibitors cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology.

The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side-effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis

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… J Clin Oncol 2015 ; 33 : 1136 – 1142 . 25713436 10.1200/JCO.2014.58.7782 PMC5657012 34 Baselga J Cortes J Kim SB Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer . …

Novel B55α-PP2A mutations in AML promote AKT T308 phosphorylation and sensitivity to AKT inhibitor-induced growth arrest.

Activation of the Protein Kinase B (PKB), or AKT pathway has been shown to correlate with acute myeloid leukemia (AML) prognosis. B55α-Protein Phosphatase 2A (PP2A) has been shown to dephosphorylate AKT at Thr-308 rendering it inactive. In fact, low expression of the PP2A regulatory subunit B55α was associated with activated phospho-AKT and correlated with inferior outcomes in AML. Despite this fact, no studies have specifically demonstrated a mechanism whereby B55α expression is regulated in AML. In this study, we demonstrate novel loss of function mutations in the PPP2R2A gene identified in

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… Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J HEMATOL Oncol. 2014;7:1. doi: 10.1186/1756-8722-7-1. 20. …

Cytokine-induced killer (CIK) cells: from basic research to clinical translation.

The accumulation of basic researches and clinical studies related to cytokine-induced killer (CIK) cells has confirmed their safety and feasibility in treating malignant diseases. This review summarizes the available published literature related to the biological characteristics and clinical applications of CIK cells in recent years. A number of clinical trials with CIK cells have been implemented during the progressive phases of cancer, presenting potential widespread applications of CIK cells for the future. Furthermore, this review briefly compares clinical applications of CIK cells with th

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… The antitumor effects of CIK cells combined with docetaxel against drug-resistant lung adenocarcinoma cell line SPC-A1/DTX in vitro and in vivo. Cancer Biother Radiopharm. 2009;24:91–98. doi: 10.1089/cbr.2008.0533. …

Antioxidant Food Supplementation in Cancer: Lessons from Clinical Trials and Insights from Preclinical Studies.

Food antioxidant supplementation has been widely proposed for cancer prevention and adjuvant therapy due to the pleiotropic role of antioxidants. Herein, particular attention is given to recent clinical trials based on the use of dietary supplements in cancer patients, both as monotherapy and in combination with standard treatments, exploring both their potential benefits and risks. This review focuses on the efficacy of the most important food antioxidants, highlighting how their action may change depending on different factors such as cancer type, dose, timing of administration and antioxida

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… continuing throughout RT and for an additional 2 weeks following completion of RT) | RT | 79 (early-stage or ductal carcinoma in situ) | [ 38 ] - Vitamin D (10,000 IU and 1000 mg of calcium each day for 4 months) | Biphosphonate | 40 (bone metastatic breast cancer) | [ 39 ] - Curcumin (6 g/day for 7 days) | Docetaxel … Curcumin’s effect in advanced and metastatic breast cancer patients treated with first or second-line docetaxel: A randomized trial Health Sci. Rep. 2024 7 e70052 10.1002/hsr2.70052 39286738 PMC11403303 41. Tirgar A. Rezaei M. Ehsani M. Salmani Z. Rastegari A. Jafari E. Khandani B.K. Nakhaee N. …

Targeting myeloid villains in the treatment with immune checkpoint inhibitors in gastrointestinal cancer.

Despite the clinical outcomes being extremely limited, blocking immune inhibitory checkpoint pathways has been in the spotlight as a promising strategy for treating gastrointestinal cancer. However, a distinct strategy for the successful treatment is obviously needed in the clinical settings. Myeloid cells, such as neutrophils, macrophages, dendritic cells, and mast cells, are the majority of cellular components in the human immune system, but have received relatively less attention for the practical implementation than T cells and NK cells in cancer therapy because of concentration of the int

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… In late 1990’s, docetaxel, paclitaxel, and irinotecan were clinically developed, showing a survival benefit compared with the best supportive care as the second line treatment ( 42 ). Recently, trifluridine tipiracil prolonged survival as the third or later line treatment ( 43 ). … The ATTRACTION-3 study that is an international randomized phase III study reported that nivolumab provided significant better prognosis as compared to chemotherapy (docetaxel or paclitaxel) (median OS = 10.9 versus 8.5 months, HR = 0.79, P = 0.0264; 3-year OS rates = 15.3% versus 8.7%) in patients with …

Cancer Vaccines for Triple-Negative Breast Cancer: A Systematic Review.

Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the poorest outcomes, and is associated with a high risk of relapse and metastasis. The treatment choices for this malignancy have been confined to conventional chemotherapeutic agents, due to a lack of expression of the canonical molecular targets. Immunotherapy has been recently changing the treatment paradigm for many types of tumors, and the approach of evoking active immune responses in the milieu of breast tumors through cancer vaccines has been introduced as one of the most novel immunotherapeutic approaches. Acco

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… Non-randomized trials are marked with asterisks. 1 HER2: human epidermal growth factor receptor 2; 2 GM-CSF: granulocyte-macrophage colony-stimulating factor; 3 BC: breast cancer; 4 DFS: disease-free survival; 5 IR: immune response; 6 MUC1: mucin 1; 7 E: epirubicin; 8 C: cyclophosphamide; 9 D: docetaxel … year; 8 DFS: disease-free survival; 9 HR: hazard ratio; 10 AE: adverse event; 11 N/S: not specified; 12 pt: patient; 13 RR: recurrence risk; 14 LD: loading dose; 15 MD: maintenance dose; 16 IHC: immunohistochemistry; 17 NAC: neoadjuvant chemotherapy; 18 E: epirubicin; 19 C: cyclophosphamide; 20 D: docetaxel …

Role of myeloid-derived suppressor cells in tumor recurrence.

The establishment of primary tumor cells in distant organs, termed metastasis, is the principal cause of cancer mortality and is a crucial therapeutic target in oncology. Thus, it is critical to establish a better understanding of metastatic progression for the future development of improved therapeutic approaches. Indeed, such development requires insight into the timing of tumor cell dissemination and seeding of distant organs resulting in occult lesions. Following dissemination of tumor cells from the primary tumor, they can reside in niches in distant organs for years or decades, following

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… sites [ 193 ] Sildenafil MM and HNSCC NCT02466802 , restored T-cell proliferation in PBMC [ 329 ] Arginase inhibitors CB-1158 Lung cancer ↑ T-cell proliferation in patient-derived G-MDSC-conditioned media [ 202 ] CRC Demonstrated minimal treatment-related toxicities [ 203 ] iNOS inhibitors L-NMMA + docetaxel … In preclinical studies, HuMax-IL8 has been shown to significantly inhibit MDSC recruitment and to improve CTL activity when given in combination with docetaxel [ 242 ]. …

New landscapes and horizons in hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC), is the sixth most frequent form of cancer and leads to the fourth highest number of deaths each year. HCC results from a combination of environmental factors and aging as there are driver mutations at oncogenes which occur during aging. Most of HCCs are diagnosed at advanced stage preventing curative therapies. Treatment in advanced stage is a challenging and pressing problem, and novel and well-tolerated therapies are urgently needed. We will discuss further advances beyond sorafenib that target additional signaling pathways and immune checkpoint proteins. The

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… The effects of combining the EGFR inhibitor erlotinib with the chemotherapeutic drug docetaxel have been examined in the NCT00532441 phase II clinical trial [ 30 ]. … In this study, combining erlotinib with docetaxel did not appear to result in enhancement of survival in comparison to patients treated with erlotinib by itself. …