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Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies.

Despite the success of targeted therapies in cancer treatment, therapy-induced resistance remains a major obstacle to a complete cure. Tumor cells evade treatments and relapse via phenotypic switching driven by intrinsic or induced cell plasticity. Several reversible mechanisms have been proposed to circumvent tumor cell plasticity, including epigenetic modifications, regulation of transcription factors, activation or suppression of key signaling pathways, as well as modification of the tumor environment. Epithelial-to-mesenchymal transition, tumor cell and cancer stem cell formation also serv

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… Completed NCT02454933 (CAURAL) | NSCLC | Durvalumab + Osimertinib | NSCLC patients with progression after EGFR-TKIs, T790M positive | 344 | I | Active, not recruiting NCT02574078 (CheckMate 370) | NSCLC | Nivolumab + Erlotinib + Crizotinib + Bevacizumab + Pemetrexed + Nab-Paclitaxel + Paclitaxel + Docetaxel … Table 2 Ongoing clinical trials of combination treatment with EMT-modulating agents Clinical trial (NCT identifier) Conditions Treatments Patients n Phase States NCT02922777 NSCLC Bemcentinib + Docetaxel Previously treated patients with advanced NSCLC 23 I Active, not recruiting NCT02488408 AML Bemcentinib …

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia.

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estim

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… The cytotoxic Docetaxel replaced mitoxantrone as the first line of care in 2004 after the Southwest Oncology Group reported that its administration with estramustine significantly extended progression-free and overall survival for CRPC patients, when compared to mitoxantrone with prednisone [ 118 ]. … However, until 2010, physicians have no other life-prolonging second-line options after the failure of docetaxel. …

Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers: a potential novel target?

In the last decades the survival of metastatic gastrointestinal (GI) cancer patients could have been significantly extended due to the introduction of targeted- and immunotherapy. However, only the minority of patients will experience long-lasting survival. Hence, novel therapeutics are clearly necessary for GI cancer patients. Molecular high-throughput profiling techniques have revealed potential novel targetable molecular alterations, emphasizing the necessity for tailored therapeutic approaches. Nuclear export proteins, particularly Exportin-1 (XPO1), have emerged as promising targets in ca

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… for Non-small Cell Lung Cancer (NSCLC) Phase I–II NCT03095612 Non-small cell lung cancer Drug: Selinexor Drug: Docetaxel A study of evaluating the safety and efficacy of ATG-010 in relapsed refractory multiple myeloma (MARCH) Phase II NCT03944057 Relapse/refractory multiple myeloma Drug: ATG-010 Selinexor … for Non-small Cell Lung Cancer (NSCLC) | Phase I–II | NCT03095612 | Non-small cell lung cancer | Drug: Selinexor Drug: Docetaxel | A study of evaluating the safety and efficacy of ATG-010 in relapsed refractory multiple myeloma (MARCH) | Phase II | NCT03944057 | Relapse/refractory multiple myeloma …

Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.

Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway - has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequ

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… in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer | Active, not recruiting | Advanced NSCLC | Drug: Docetaxel, Trametinib | Phase II NCT02231775 | Dabrafenib and Trametinib Before and After Surgery in Treating Patients With Stage IIIB-C Melanoma With BRAF … in Patients Receiving 2nd Line Treatment for v-Kiras2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Positive NSCLC | Active, not recruiting | Advanced or metastatic NSCLC | Drug: Selumetinib, Docetaxel, Pegylated GCSF | Phase III NCT01909453 | Study Comparing Combination of LGX818 Plus MEK162 Versus …

Мельфаланский змеиный надвенный гиперпигментация с сопутствующим венозным тромбозом.

Serpentin suprevenus гиперпигментация (SSH) — редкая резиновая негативная реакция, характеризующаяся линейной гиперпигментацией вдоль поверхностных вен после внутривенной наркотерапии, чаще всего химиотерапией. Мы сообщаем о редком случае SSH, вызванном мелфаланом, который осложняется поверхностным венозным тромбозом. A 54-year-old человек, лечившийся от светоцепных миэломы, разработал асимптомные серпигинозные гиперпигированные повреждения вдоль поверхностной венозной сети one Через день после внутривенного инъекции мелфала до аутологической трансплантации стволовых клеток. Ten Через нескольк

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… However, a wide range of chemotherapeutic drugs have been implicated, including taxanes such as docetaxel, vinca alkaloids such as vinorelbine and vincristine, alkylating agents such as carboplatin and oxaliplatin, antitumor antibiotics such as actinomycin and bleomycin, anthracyclines such as epirubicin …

Antibody-Drug Conjugates and Peptide-Drug Conjugates: Current Understandings and Future Perspectives.

Antibody-drug conjugates (ADCs) and peptide-drug conjugates (PDCs) are modular targeted therapeutics in which molecular recognition is coupled with controlled payload delivery. Owing to their high specificity and precision, they have been regarded as a transformative paradigm for cancer therapy. In this review, current understandings and future perspectives of ADCs and PDCs are synthesized across rational design principles, historical evolution, clinical translation, and emerging formats, aiming to improve practical comprehension and application in oncology. Key determinants of performance: ta

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… In patients with EGFR‐mutated advanced or metastatic NSCLC after previous treatment failure with EGFR‐tyrosine kinase inhibitors (EGFR‐TKI) and platinum based chemotherapy, sacituzumab tirumotecan also demonstrated encouraging efficacy compared with docetaxel [ 167 ]. … 280 ] | EphA2 | Bicyclic peptide | MMAE | Advanced solid tumors historically known for expression of EphA2 | Phase I/II | NCT04180371 BT8009 [ 281 ] | Nectin‐4 | Bicyclic peptide | MMAE | Locally advanced or metastatic urothelial cancer | Phase II/III | NCT06225596 TH1902 [ 282 ] | SORT1 | TH19P02 | Docetaxel …

Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.

Since the United States Food and Drug Administration approved the first immune checkpoint inhibitor ipilimumab for metastatic melanoma in 2011, ICIs have been approved for a range of cancers and significantly improving treatment outcomes. However, the objective response rate of ICI monotherapy remains modest (10-40%), with clinical benefit observed in only 15-20% of patients. The limited efficacy of ICIs in many patients is often attributed to poorly immunogenic ("cold") tumors. Radiotherapy and chemotherapy exhibit immunomodulatory properties that can enhance tumor immunogenicity. These effec

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… Certain agents (e.g., docetaxel, low‐dose cyclophosphamide) selectively deplete proliferating Treg cells, with sustained effects achievable through intermittent low‐dose regimens. … In a study by Li et al. [ 239 ], Treg cells were significantly elevated in the peripheral blood of NSCLC patients compared with healthy individuals, and docetaxel was found to deplete activated Treg cells, thereby alleviating the immunosuppressive microenvironment [ 239 ]. …

Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison.

Emerging tumor immunotherapy methods encompass bispecific antibodies (BSABs), immune checkpoint inhibitors (ICIs), and adoptive cell immunotherapy. BSABs belong to the antibody family that can specifically recognize two different antigens or epitopes on the same antigen. These antibodies demonstrate superior clinical efficacy than monoclonal antibodies, indicating their role as a promising tumor immunotherapy option. Immune checkpoints are also important in tumor immunotherapy. Programmed cell death protein-1 (PD-1) is a widely acknowledged immune checkpoint target with effective anti-tumor ac

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… In another study of patients with advanced BC, zanidatamab combined with 75 mg/m 2 of docetaxel as first-line therapy resulted in an ORR of 86.4% and a 6-month PFS rate of 90.9%, highlighting its significant anti-tumor activity [ 168 ]. … Furthermore, zanidatamab combined with docetaxel showed more significant antitumor activity than zanidatamab monotherapy (ORR, 86.4%; 6-month PFS rate, 90.9%) [ 168 ]. …

Effects of exercise on inflammation in patients receiving chemotherapy: a nationwide NCORP randomized clinical trial.

PurposeA growing body of research suggests that inflammation plays a role in many chemotherapy-related toxicities such as fatigue, anxiety, and neuropathy. Regular exercise can change levels of individual cytokines (e.g., reducing IL-6, increasing IL-10); however, it is not known whether exercise during chemotherapy affects relationships between cytokines (i.e., whether cytokine concentrations change collectively vs. independently). This study assessed how 6 weeks of exercise during chemotherapy affected relationships between changes in concentrations of several cytokines.MethodsThis is a seco

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… The three most common chemotherapy regimen types were cyclophosphamide + doxorubicin, cyclophosphamide + docetaxel/paclitaxel, and carboplatin + docetaxel/paclitaxel. There were no significant baseline differences between patients in the two study arms. Intervention adherence. …

International comparison of the factors influencing reimbursement of targeted anti-cancer drugs.

BackgroundReimbursement policies for anti-cancer drugs vary among countries even though they rely on the same clinical evidence. We compared the pattern of publicly funded drug programs and analyzed major factors influencing the differences.MethodsWe investigated reimbursement policies for 19 indications with targeted anti-cancer drugs that are used variably across ten countries. The available incremental cost-effectiveness ratio (ICER) data were retrieved for each indication. Based on the comparison between actual reimbursement decisions and the ICERs, we formulated a reimbursement adequacy i

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… fluorouracil, and folinic acid | 2010 | No | 2009 | 2009 | 2010 | No | No | No | 2009 | 2012 | Head and neck cancer (squamous cell carcinoma) : 1st line with platinum-based chemotherapy | 2007 | 2011 | 2010 | No | No | No | No | 2009 | No | 2011 Crizotinib | NSCLC ( ALK fusion positive): 2nd line (vs. docetaxel … chronic phase: 1st-line | 118,050 Cetuximab | Colorectal cancer: with irinotecan | 121,528 Temsirolimus | Renal cell carcinoma: 1st-line for poor prognosis patients | 128,595 Bevacizumab | Renal cell carcinoma: 1st line with interferon-α | 131,070 Crizotinib | NSCLC ( ALK fusion positive): 2nd line (vs. docetaxel …

Clinical experience with Zarzio® in Europe: what have we learned?

Biosimilars are similar, but non-identical, versions of existing biological drugs for which patents have expired. Despite the rigorous approval process for biosimilars, concerns have been expressed about the efficacy and safety of these products in clinical practice. Biosimilars of filgrastim, based on the originator product Neupogen®, have been available since 2008 and are now in widespread clinical use in Europe and elsewhere. Three biosimilar G-CSFs have been approved based on a combination of physicochemical and biological protein characterisation, pharmacokinetic and pharmacodynamic asses

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… The study was conducted in 170 patients with stage II–IV breast cancer receiving cytotoxic chemotherapy with doxorubicin (60 mg/m 2 ) and docetaxel (75 mg/m 2 ). … Pharmacol Ther 2009 47 275 282 19356394 10.5414/cpp47275 20. del Giglio A Eniu A Ganea-Motan D Topuzov E Lubenau H XM02 is superior to placebo and equivalent to Neupogen in reducing the duration of severe neutropenia and the incidence of febrile neutropenia in cycle 1 in breast cancer patients receiving docetaxel …

Keeping Up to Date in a New Era of Oncology.

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… Two case reports delve into unique adverse event management: one on concurrent ocular and dermatologic toxicities from docetaxel, and another on capecitabine-associated hand-foot syndrome. …

The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.

Ubiquitin Proteasome System (UPS) is an adaptable and finely tuned system that sustains proteostasis network under a large variety of physiopathological conditions. Its dysregulation is often associated with the onset and progression of human diseases; hence, UPS modulation has emerged as a promising new avenue for the development of treatments of several relevant pathologies, such as cancer and neurodegeneration. The clinical interest in proteasome inhibition has considerably increased after the FDA approval in 2003 of bortezomib for relapsed/refractory multiple myeloma, which is now used in

A review of immunotherapy for bone tumors.

This article reviews the latest research progress in immunotherapy for bone tumors. Bone tumors are a serious threat to human health, and traditional treatments have limitations. Recently, immunotherapy, as an emerging treatment method, has shown great potential in the treatment of bone tumors. This article systematically introduces the pathological features, traditional treatment methods and limitations of bone tumors, and focuses on the principles, application status and challenges of immune checkpoint inhibitors, CAR-T cell therapy, tumor vaccines and other immunotherapies. At the same time

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… Standard treatment for metastatic disease revolves around anthracycline-based chemotherapy, but other drugs including Dacarbazine ( 39 )、Gemcitabine/docetaxel ( 40 )、Ifosfamide ( 41 )、Trabectedin ( 42 )、Pazobanide ( 43 ) and Eribulin ( 44 ) may be used. … Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected . …

Exploring cellular diversity in lung adenocarcinoma epithelium: Advancing prognostic methods and immunotherapeutic strategies.

Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single-cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learnin

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… Atezolizumab versus docetaxel in patients with previously treated non‐small‐cell lung cancer (OAK): a phase 3, open‐label, multicentre randomised controlled trial . … Atezolizumab versus docetaxel for patients with previously treated non‐small‐cell lung cancer (POPLAR): a multicentre, open‐label, phase 2 randomised controlled trial . Lancet . 2016 ; 387 ( 10030 ): 1837 ‐ 1846 . 26970723 10.1016/S0140-6736(16)00587-0 21 Cao Y , Fu L , Wu J , et al. …

Studies to Assess the Utility of Serum Neurofilament Light Chain as a Biomarker in Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and disabling dose-limiting toxicities of chemotherapy. We report here the results of two separate non-interventional studies (49 patients), which evaluated blood neurofilament light chain (NfL) as a biomarker of CIPN in breast cancer patients treated with paclitaxel. All patients underwent a standard treatment protocol that was established independently of the present studies. NfL was measured in serum using an ultrasensitive single-molecule array and compared with the self-administered European Organization for Resea

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… Epiphany is an ongoing prospective natural history study of CIPN in patients receiving taxanes (paclitaxel, docetaxel) for breast cancer, bortezomib for multiple myeloma, oxaliplatin-based regimens for colorectal cancer, or vincristine for lymphoma. … expectancy ≥ 6 months, (3) patients with NCI-CTCAE grade 0 CIPN (with the exception of patients with multiple myeloma treated with bortezomib, NCI-CTCAE grade ≤ 1), (4) Eastern Cooperative Oncology Group performance status of 0–2, and patients with (5a) breast cancer beginning treatment with paclitaxel or docetaxel …

A Systematic Review of Nutritional Lab Correlates with Chemotherapy Induced Peripheral Neuropathy.

Chemotherapy induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy for which no prevention or cure exists. Cancer and cancer treatments can adversely affect nutritional status. Nutrition may play a role in development of CIPN, yet the relationship between nutrition and CIPN is not well understood. Common laboratory values measuring various aspects of nutrition (hemoglobin/hematocrit, vitamin B12, calcium, and magnesium) may be associated with CIPN. The aim of this systematic review is to evaluate the empirical evidence surrounding the relationship between laborato

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… One of the studies also included persons with other malignancies who were receiving cisplatin, paclitaxel, or docetaxel. A prospective evaluation of 130 participants in Iran who were receiving oxaliplatin for colorectal cancer demonstrated an overall prevalence of hypomagnesemia of 13.8% [ 14 ]. … In a prospective study that included 113 persons receiving oxaliplatin, cisplatin, paclitaxel, or docetaxel, no significant relationships between CIPN and magnesium levels were identified. This may have been due to the heterogeneity of chemotherapy drugs included in the study. …

Clinical Trial Evidence Supporting US Food and Drug Administration Approval of Novel Cancer Therapies Between 2000 and 2016.

IMPORTANCE: Clinical trial evidence used to support drug approval is typically the only information on benefits and harms that patients and clinicians can use for decision-making when novel cancer therapies become available. Various evaluations have raised concern about the uncertainty surrounding these data, and a systematic investigation of the available information on treatment outcomes for cancer drugs approved by the US Food and Drug Administration (FDA) is warranted. OBJECTIVE: To describe the clinical trial data available on treatment outcomes at the time of FDA approval of all novel c

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… Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non–small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. …

Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis; Extensive Review of Reports of Drug-Induced Etiologies, and Possible Therapeutic Modalities.

Stevens - Johnson Syndrome and Toxic Epidermal Necrolysis are adverse hypersensitivity reactions that affect the skin and mucous membranes. They are characterised by erythematous macules and hemorrhagic erosions of the mucous membranes. Epidermal detachments of varying degrees of severity also occur in these conditions. Various aetiologies are associated with these conditions, with adverse drug reaction being the most common. Though the worldwide incidence of these conditions is recorded as low, diverse types of medication are being observed to lead to these conditions. This review compiles in

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… Docetaxel: Due to its strong toxicity, a patient presented with SJS after its use as a chemotherapeutic agent. Skin eruptions erupted after the first cycle of chemotherapy [ 59 ]. … doi.org/10.5125/jkaoms.2017.43.1.57 PMid:28280713 PMCid: PMC5342976 28280713 10.5125/jkaoms.2017.43.1.57 PMC5342976 58 Hiraki Stevens-Johnson Syndrome Induced by Paclitaxel in a Patient with Squamous Cell Carcinoma of the Lung Anticancer research 2004 24 1135 1138 PMid:15154637 15154637 59 Sawada Y Docetaxel-induced …

Recent advances in drug repositioning for the discovery of new anticancer drugs.

Drug repositioning (also referred to as drug repurposing), the process of finding new uses of existing drugs, has been gaining popularity in recent years. The availability of several established clinical drug libraries and rapid advances in disease biology, genomics and bioinformatics has accelerated the pace of both activity-based and in silico drug repositioning. Drug repositioning has attracted particular attention from the communities engaged in anticancer drug discovery due to the combination of great demand for new anticancer drugs and the availability of a wide variety of cell- and targ

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… PMC43727 7 Singhal S Mehta J Desikan R Ayers D Roberson P Eddlemon P Antitumor activity of thalidomide in refractory multiple myeloma N Engl J Med 1999 341 1565 71 10564685 10.1056/NEJM199911183412102 8 Ning YM Gulley JL Arlen PM Woo S Steinberg SM Wright JJ Phase II trial of bevacizumab, thalidomide, docetaxel … endoplasmic reticulum stress, autophagy, and apoptosis in vitro and in vivo Clin Cancer Res 2007 13 5183 94 17785575 10.1158/1078-0432.CCR-07-0161 33 Yang Y Ikezoe T Nishioka C Bandobashi K Takeuchi T Adachi Y NFV, an HIV-1 protease inhibitor, induces growth arrest, reduced Akt signalling, apoptosis and docetaxel …