Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma

Cancers, Год журнала: 2021, Номер 13(14), С. 3540 - 3540

Опубликована: Июль 15, 2021

Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast cancer patients was introduced in 1998. Although trastuzumab has opened new avenue to treat with and other types cancer, some are not responsive or become resistant this treatment. So far, several mechanisms have been suggested mode action trastuzumab; however, findings regarding these controversial. In review, we aimed provide detailed insight into various trastuzumab.

Язык: Английский

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The effects of metformin on autophagy

Biomedicine & Pharmacotherapy, Год журнала: 2021, Номер 137, С. 111286 - 111286

Опубликована: Янв. 30, 2021

Metformin is the first-line option for treating newly diagnosed diabetic patients and also involved in other pharmacological actions, including antitumor effect, anti-aging polycystic ovarian syndrome prevention, cardiovascular action, neuroprotective etc. However, mechanisms of metformin actions were not fully illuminated. Recently, increasing researches showed that autophagy a vital medium playing actions. Nevertheless, results on effects inconsistent. Apart from few clinical evidences, more data focused kinds no-clinical models. First, many studies could induce via number signaling pathways, AMPK-related pathways (e.g. AMPK/mTOR, AMPK/CEBPD, MiTF/TFE, AMPK/ULK1, AMPK/miR-221), Redd1/mTOR, STAT, SIRT, Na+/H+ exchangers, MAPK/ERK, PK2/PKR/AKT/ GSK3β, TRIB3. Secondly, some process inhibiting autophagy, such as (AMPK/NF-κB undetermined pathways), Hedgehog, miR-570-3p, miR-142-3p, MiR-3127-5p. Thirdly, two types PI3K/AKT/mTOR endoplasmic reticulum (ER) stress bidirectionally impact effectiveness autophagy. Finally, multiple signal reviewed collectively terms affecting The combining its discussed. It would help better apply to treat diseases term mediating

Язык: Английский

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Free Radicals and Oxidative Stress: Signaling Mechanisms, Redox Basis for Human Diseases, and Cell Cycle Regulation

Current Molecular Medicine, Год журнала: 2021, Номер 23(1), С. 13 - 35

Опубликована: Дек. 24, 2021

Free radicals contain one or more unpaired electrons in their valence shell, thus making them unstable, short-lived, and highly reactive species. Excessive generation of these free ultimately leads to oxidative stress causing oxidation damage significant macromolecules the living system essentially disrupting signal transduction pathways antioxidants equilibrium. At lower concentrations, ROS serves as "second messengers," influencing many physiological processes cell. However, higher concentrations beyond cell capacity cause stress, contributing human pathologies such diabetes, cancer, Parkinson's disease, cardiovascular diseases, cataract, asthma, hypertension, atherosclerosis, arthritis, Alzheimer's disease. Signaling NF-κB, MAPKs, PI3K/Akt/ mTOR, Keap1-Nrf2- ARE modulate detrimental effects by increasing expression cellular antioxidant defenses, phase II detoxification enzymes, decreased production ROS. H2O2 are indeed needed for advancement cycle molecules influence DNA, proteins, enzymes pathway. In course progression, redox environment becomes oxidized, moving from G1 phase, becoming G2/M moderate S phase. Signals form an increase pro-oxidant levels required, signals often terminated a rise amount MnSOD with decrease level cyclin D1 proteins. Therefore, understanding mechanism regulation will help therapy diseases.

Язык: Английский

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Long non-coding RNAs: Biogenesis, functions, and clinical significance in gastric cancer

Molecular Therapy — Oncolytics, Год журнала: 2021, Номер 23, С. 458 - 476

Опубликована: Ноя. 11, 2021

Gastric cancer (GC) is one of the most prevalent malignant tumor types and third leading cause cancer-related death worldwide. Its morbidity mortality are very high due to a lack understanding about its pathogenesis slow development novel therapeutic strategies. Long non-coding RNAs (lncRNAs) class with length more than 200 nt. They play crucial roles in wide spectrum physiological pathological processes by regulating expression genes involved proliferation, differentiation, apoptosis, cell cycle, invasion, metastasis, DNA damage, carcinogenesis. The aberrant lncRNAs has been found various types. A growing amount evidence demonstrates that many aspects GC pathogenesis, including occurrence, recurrence, indicating their potential role as biomarkers diagnosis, prognosis, targets GC. This review systematically summarizes biogenesis, biological properties, functions highlights critical clinical significance information may contribute better diagnostics treatments for

Язык: Английский

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Metastasis and MAPK Pathways

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(7), С. 3847 - 3847

Опубликована: Март 31, 2022

Cancer is a leading cause of death worldwide. In many cases, the treatment disease limited due to metastasis cells distant locations body through blood and lymphatic drainage. Most anticancer therapeutic options focus mainly on inhibition tumor cell growth or induction death, do not consider molecular basis metastasis. The aim this work provide comprehensive review focusing cancer mitogen-activated protein kinase (MAPK) pathway (ERK/JNK/P38 signaling) as crucial modulator process.

Язык: Английский

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Zinc: From Biological Functions to Therapeutic Potential

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(5), С. 4822 - 4822

Опубликована: Март 2, 2023

The trace element zinc (Zn) displays a wide range of biological functions. Zn ions control intercellular communication and intracellular events that maintain normal physiological processes. These effects are achieved through the modulation several Zn-dependent proteins, including transcription factors enzymes key cell signaling pathways, namely those involved in proliferation, apoptosis, antioxidant defenses. Efficient homeostatic systems carefully regulate concentrations. However, perturbed homeostasis has been implicated pathogenesis chronic human diseases, such as cancer, diabetes, depression, Wilson’s disease, Alzheimer’s other age-related diseases. This review focuses on Zn’s roles survival/death, DNA repair mechanisms, outlines some targets, addresses therapeutic potential supplementation

Язык: Английский

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A Review of Gut Microbiota‐Derived Metabolites in Tumor Progression and Cancer Therapy

Advanced Science, Год журнала: 2023, Номер 10(15)

Опубликована: Март 23, 2023

Abstract Gut microbiota‐derived metabolites are key hubs connecting the gut microbiome and cancer progression, primarily by remodeling tumor microenvironment regulating signaling pathways in cells multiple immune cells. The use of microbial radiotherapy chemotherapy mitigates severe side effects from treatment improves efficacy treatment. Immunotherapy combined with effectively activates system to kill tumors overcomes drug resistance. Consequently, various novel strategies have been developed modulate metabolites. Manipulation genes involved metabolism using synthetic biology approaches directly affects levels metabolites, while fecal transplantation phage affect altering composition microbiome. However, some harbor paradoxical functions depending on context (e.g., type cancer). Furthermore, metabolic microorganisms certain anticancer drugs such as irinotecan gemcitabine, render ineffective or exacerbate their adverse effects. Therefore, a personalized comprehensive consideration patient's condition is required when employing treat cancer. purpose this review summarize correlation between cancer, provide fresh ideas for future scientific research.

Язык: Английский

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Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies

Journal of Hematology & Oncology, Год журнала: 2022, Номер 15(1)

Опубликована: Апрель 12, 2022

Abstract Triple-negative breast cancer (TNBC) is a subtype of human with one the worst prognoses, no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed (PCD), has been widely reported to have numerous links progression and therapy many types cancer. Of note, RCD can be divided into different subroutines, including autophagy-dependent death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis anoikis. More recently, targeting subroutines small-molecule compounds emerging promising strategy, which rapidly progressed in treatment TNBC. Therefore, this review, we focus on summarizing molecular mechanisms above-mentioned seven major related TNBC latest progress subroutines. Moreover, further discuss combined drug (e.g., narciclasine) or more drugs torin-1 chloroquine) achieve potential by regulating importantly, demonstrate several ONC201 NCT03733119) clinical trials. Taken together, these findings will provide clue illuminating actionable low-hanging-fruit druggable targets candidate for RCD-related therapies. Graphical abstract

Язык: Английский

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The Role of Silver Nanoparticles in the Diagnosis and Treatment of Cancer: Are There Any Perspectives for the Future?

Life, Год журнала: 2023, Номер 13(2), С. 466 - 466

Опубликована: Фев. 7, 2023

Cancer is a fatal disease with complex pathophysiology. Lack of specificity and cytotoxicity, as well the multidrug resistance traditional cancer chemotherapy, are most common limitations that often cause treatment failure. Thus, in recent years, significant efforts have concentrated on development modernistic field called nano-oncology, which provides possibility using nanoparticles (NPs) aim to detect, target, treat diseases. In comparison conventional anticancer strategies, NPs provide targeted approach, preventing undesirable side effects. What more, nanoparticle-based drug delivery systems shown good pharmacokinetics precise targeting, reduced resistance. It has been documented that, cells, promote reactive oxygen species (ROS) production, induce cell cycle arrest apoptosis, activate ER (endoplasmic reticulum) stress, modulate various signaling pathways, etc. Furthermore, their ability inhibit tumor growth vivo also documented. this paper, we reviewed role silver (AgNPs) nanomedicine, discussing numerous mechanisms by they render properties under both vitro conditions, potential diagnosis cancer.

Язык: Английский

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Targeting PI3K/AKT/mTOR Signaling Pathway in Pancreatic Cancer: From Molecular to Clinical Aspects

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(17), С. 10132 - 10132

Опубликована: Сен. 4, 2022

Although pancreatic cancer (PC) was considered in the past an orphan type due to its low incidence, it may become future one of leading causes death. Pancreatic ductal adenocarcinoma (PDAC) is most frequent PC, being a highly aggressive malignancy and having 5-year survival rate less than 10%. Non-modifiable (family history, age, genetic susceptibility) modifiable (smoking, alcohol, acute chronic pancreatitis, diabetes mellitus, intestinal microbiota) risk factors are involved PC pathogenesis. Chronic inflammation induced by various plays crucial roles development from initiation metastasis. In multiple malignant conditions such as cytokines, chemokines, growth activate class I phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target rapamycin (mTOR) (PI3K/AKT/mTOR) signaling pathway, which key cell growth, survival, proliferation, metabolism, motility. Currently, mTOR, AKT, PI3K inhibitors used clinical studies. Moreover, PI3K/mTOR dual tested vitro vivo with promising results for patients. The main aim this review present factors, tumor microenvironment development, PI3K/AKT/mTOR dysregulation clinical, vivo,

Язык: Английский

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