Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology DOI Creative Commons
Shuang Ma, Ying Lü,

S.J. Sui

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides comprehensive review of methodologies for evaluating including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, single-fiber experiments to assess quality performance. Furthermore, it elucidates mechanisms, applications, limitations various modalities, immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, combined chemoimmunotherapy, while examining their effects on function systemic responses. Key findings indicate that although is effective in augmenting antitumor immunity, frequently induces muscle-related adverse such as weakness, fatigue, or damage, primarily mediated by cytokine release activation. underscores significance niches within microenvironment influencing treatment outcomes proposes strategies optimize therapy through personalized regimens combinatorial approaches. highlights need further formation interactions muscle-tumor. Our crucial advancing efficacy immunotherapy, reducing effects, ultimately improving survival rates life patients with cancer.

Язык: Английский

PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells DOI Creative Commons

Magalie Hervieu,

Arnaud J. Legrand, Emilie Floquet

и другие.

Cancer Reports, Год журнала: 2025, Номер 8(1)

Опубликована: Янв. 1, 2025

The Ets-1 transcription factor plays a primordial role in regulating the expression of numerous genes implicated cancer progression. In previous study, we revealed that poly(ADP-ribose) polymerase-1 (PARP-1) inhibition by PJ-34 results level increase cells, which is related with cell death Ets-1-expressing cells. mechanism antitumor effect PARP-1 was investigated MDA-MB-231 breast We tested effects four PARP inhibitors (PARPi) (PJ-34, Veliparib, Olaparib, and Rucaparib). first demonstrated PARPi reduced cells growth through G2/M cycle arrest. Next, evaluated on oxidative DNA damage Ets-1-overexpressing Ets-1-non-expressing showed led only to accumulate it, triggers response as panel damage-related proteins. Importantly, increased reactive oxygen species (ROS), this accompanied upregulation p47phox expression, subunit NAPDH oxidase (NOX). These preliminary findings correlate PARPi-induced damage/oxidative stress

Язык: Английский

Процитировано

0
iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer DOI Creative Commons

María del Moral-Martinez,

Paula Sánchez-Uceta,

Ruben Clemente-Gonzalez

и другие.

Biomolecules, Год журнала: 2025, Номер 15(1), С. 125 - 125

Опубликована: Янв. 14, 2025

PARP-1 has been linked to the progression of several types cancer. We have recently reported that influences tumor in CRC through regulation CSCs a p53-dependent manner. In this study, we propose nitric oxide (NO) produced by inducible synthase (iNOS) could act as mediator. evaluated expression iNOS cohort patients previously used analyze effects on relation p53 status. also developed an vitro model which was stably overexpressed. patients, correlated with differentiation grade, and high CSC markers, although only wild-type tumors, found for PARP-1. vitro, overexpression induced increased growth stemness cells, while exerting opposite effect mutated ones, expected. Treatment 1400 W, selective inhibitor iNOS, or gene silencing counteracted both cells. Given development resistance demonstrated after treatment inhibitors, be considered new therapeutic target CRC, tumors.

Язык: Английский

Процитировано

0
Current Advances in PARP1‐Targeted Theranostics DOI
Jie Tong,

Baosheng Chen,

Tommaso Volpi

и другие.

Journal of Labelled Compounds and Radiopharmaceuticals, Год журнала: 2025, Номер 68(1-2)

Опубликована: Янв. 1, 2025

Poly (ADP-ribose) polymerase 1 (PARP1) plays critical roles in DNA repair, chromatin regulation, and cellular equilibrium, positioning it as a pivotal target for therapeutic interventions cancer central nervous system (CNS) disorders. PARP1 responds to oxidative stress damage through PARylation, influencing energy depletion, survival, inflammation, genomic regulation many biological scenarios. PARP inhibitors (PARPis) have demonstrated efficacy against cancers harboring defective homologous recombination repair pathways, notably those linked BRCA mutations. PARP1-targeted PET imaging enables patient stratification, treatment assessment, PARPi pharmacodynamic evaluation other pathophysiological conditions. Importantly, theranostics emerged both diagnostic applications multiple types of cancers, representing advancement personalized oncology. However, its application brain tumors is limited by the heterogeneous integrity blood barrier (BBB) blood-tumor barrier. Thus, development BBB-penetrant tracers remains an unmet need cancers. This review summarizes current landscape radiopharmaceuticals radioligands targeting PARP1, detailing their pharmacological characteristics potential clinical uses. Furthermore, this discusses that can cross BBB, underscoring neurooncology neurological

Язык: Английский

Процитировано

0
177Lu-DOTATATE in Combination with PARP Inhibitor Olaparib Is Feasible in Patients with Somatostatin-Positive Tumors: Results from the LuPARP Phase I Trial DOI
Andreas Hallqvist,

Elva Brynjarsdóttir,

T. Krantz

и другие.

Journal of Nuclear Medicine, Год журнала: 2025, Номер unknown, С. jnumed.124.268902 - jnumed.124.268902

Опубликована: Фев. 27, 2025

This phase I trial aimed to assess the feasibility and toxicity of combining poly(adenosine diphosphate–ribose) polymerase inhibitor olaparib with 177Lu-DOTATATE in patients somatostatin receptor–positive tumors, goal enhancing treatment efficacy through inhibition tumor cell DNA repair mechanisms. Methods: Eighteen were enrolled, mostly pancreatic or small intestinal neuroendocrine tumors atypical lung carcinoids. Patients received a standard dose (7,400 MBq) for up 4 cycles, combined escalating doses (50–300 mg twice day [BID]). The primary objective was evaluate using National Cancer Institute Common Toxicity Criteria version 5.0. Secondary objectives included time progression, overall survival, response rate, dosimetry variables. Results: combination generally well tolerated. Five did not complete cycles because noncompliance, carcinoid crisis after first infusion. Among remaining patients, thrombocytopenia dose-limiting toxicity, observed 3 at 300-mg level. Other toxicities mild, predominantly low-grade bone marrow suppression, nausea, fatigue. Conclusion: study demonstrates that is feasible, primarily related thrombocytopenia. On basis findings, we recommend starting 200 BID future studies, potential escalate 300 depending on patient tolerance. Further investigation larger, randomized trials warranted clinical this optimize dosing strategies.

Язык: Английский

Процитировано

0
Common Drug-Drug and Drug-Food Interactions in Antineoplastic Agents: A short update review DOI Open Access
Sonia Sanajou, Terken Baydar

Hacettepe University Journal of the Faculty of Pharmacy, Год журнала: 2025, Номер 45(1), С. 92 - 105

Опубликована: Март 1, 2025

Cancer treatment regimens often combine chemotherapeutics, supportive therapies, and medications for comorbidities, increasing the risk of drug-drug (DDIs) drug-food interactions (DFIs). These can alter pharmacokinetics pharmacodynamics anticancer agents, potentially leading to failure, severe adverse events, or hospitalization. Elderly patients, polypharmacy, narrow therapeutic index many chemotherapeutics further compound these challenges. This review explores mechanisms underlying DDIs DFIs, focusing on absorption, metabolism, transport protein modulation—key processes influencing drug bioavailability toxicity in oncology. Clinically relevant examples are provided illustrate interactions. The underscores critical role pharmacy services identifying, preventing, managing interactions, offering actionable strategies enhance patient safety efficacy. By addressing healthcare providers mitigate risks, improve outcomes, quality life cancer patients.

Язык: Английский

Процитировано

0
Computational Design and Structural Insights into Quinazoline-Based Lead Molecules for Targeting PARP10 in Cancer Therapy DOI

Revathi Gnanavelou,

Manikandan Jayaraman,

Jeyaraman Jeyakanthan

и другие.

Journal of Molecular Graphics and Modelling, Год журнала: 2025, Номер 137, С. 109005 - 109005

Опубликована: Март 3, 2025

Язык: Английский

Процитировано

0
Targeting of the 8-oxodG Base Excision Repair Pathway for Cancer Therapy DOI Creative Commons

Anna Piscone,

Francesca Gorini, Susanna Ambrosio

и другие.

Cells, Год журнала: 2025, Номер 14(2), С. 112 - 112

Опубликована: Янв. 14, 2025

Genomic integrity is critical for cellular homeostasis, preventing the accumulation of mutations that can drive diseases such as cancer. Among mechanisms safeguarding genomic stability, Base Excision Repair (BER) pathway plays a pivotal role in counteracting oxidative DNA damage caused by reactive oxygen species. Central to this are enzymes like 8-oxoguanine glycosylase 1 (OGG1), which recognize and excise 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) lesions, thereby initiating series repair processes restore integrity. BER inhibitors have recently been identified promising approach cancer therapy, increasing sensitivity cells radiotherapy chemotherapy. By exploiting tumor-specific dependencies synthetic lethal interactions, these could be used selectively target while sparing normal cells. This review provides robust reference scientific researchers, offering an updated perspective on small-molecule targeting 8-oxodG-BER highlighting their potential expanding treatment strategies.

Язык: Английский

Процитировано

0
Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology DOI Creative Commons
Shuang Ma, Ying Lü,

S.J. Sui

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 2, 2025

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides comprehensive review of methodologies for evaluating including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, single-fiber experiments to assess quality performance. Furthermore, it elucidates mechanisms, applications, limitations various modalities, immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, combined chemoimmunotherapy, while examining their effects on function systemic responses. Key findings indicate that although is effective in augmenting antitumor immunity, frequently induces muscle-related adverse such as weakness, fatigue, or damage, primarily mediated by cytokine release activation. underscores significance niches within microenvironment influencing treatment outcomes proposes strategies optimize therapy through personalized regimens combinatorial approaches. highlights need further formation interactions muscle-tumor. Our crucial advancing efficacy immunotherapy, reducing effects, ultimately improving survival rates life patients with cancer.

Язык: Английский

Процитировано

0