Exploring treatment options in cancer: Tumor treatment strategies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июль 17, 2024

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive remarkable transformation. Emerging fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, gene therapy. These cutting-edge not only afford personalized precise targeting, but also provide enhanced comfort potential to impede disease progression. Nonetheless, it is acknowledged that these strategies still harbour untapped for further advancement. Gaining understanding merits limitations holds promise offering novel perspectives clinical practice foundational research endeavours. In this review, we discussed different modalities, including drugs, peptide antibody cell therapy, It will detailed explanation each method, addressing their status development, challenges, solutions. The aim assist clinicians researchers in gaining deeper diverse options, enabling them carry out effective advance more efficiently.

Язык: Английский

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Comprehensive review of CRISPR-based gene editing: mechanisms, challenges, and applications in cancer therapy

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Янв. 9, 2024

Abstract The CRISPR system is a revolutionary genome editing tool that has the potential to revolutionize field of cancer research and therapy. ability precisely target edit specific genetic mutations drive growth spread tumors opened up new possibilities for development more effective personalized treatments. In this review, we will discuss different CRISPR-based strategies have been proposed therapy, including inactivating genes tumor growth, enhancing immune response cells, repairing cause cancer, delivering cancer-killing molecules directly cells. We also summarize current state preclinical studies clinical trials highlighting most promising results challenges still need be overcome. Safety delivery are important therapy become viable option. limitations overcome, such as off-target effects, safety, site. Finally, provide an overview opportunities in future directions development. change landscape research, review aims overcome realize potential.

Язык: Английский

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New clinical trial design in precision medicine: discovery, development and direction

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Март 4, 2024

Abstract In the era of precision medicine, it has been increasingly recognized that individuals with a certain disease are complex and different from each other. Due to underestimation significant heterogeneity across participants in traditional “one-size-fits-all” trials, patient-centered trials could provide optimal therapy customization specific biomarkers were developed including basket, umbrella, platform trial designs under master protocol framework. recent years, successive FDA approval indications based on biomarker-guided demonstrated these new clinical ushering tremendous opportunities. Despite rapid increase number current research understanding designs, as compared remains limited. The majority focuses methodologies, there is lack in-depth insight concerning underlying biological logic designs. Therefore, we this comprehensive review discovery development their perspective medicine. Meanwhile, discuss future directions potential design view “Precision Pro”, “Dynamic Precision”, “Intelligent Precision”. This would assist trial-related researchers enhance innovation feasibility by expounding logic, which be essential accelerate progression

Язык: Английский

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Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis

European Urology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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BRCAness, DNA gaps, and gain and loss of PARP inhibitor–induced synthetic lethality

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(14)

Опубликована: Июль 14, 2024

Mutations in the tumor-suppressor genes BRCA1 and BRCA2 resulting BRCA1/2 deficiency are frequently identified breast, ovarian, prostate, pancreatic, other cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) selectively kill BRCA1/2-deficient cancer cells by inducing synthetic lethality, providing an effective biomarker-guided strategy for targeted therapy. However, a substantial fraction of patients carrying mutations do not respond to PARPis, most develop resistance PARPis over time, highlighting major obstacle PARPi therapy clinic. Recent studies have revealed that changes specific functional defects cells, particularly their suppressing protecting single-stranded DNA gaps, contribute gain or loss PARPi-induced lethality. These findings only shed light on mechanism action but also lead revised models explain how BRCA-deficient cells. Furthermore, new mechanistic principles sensitivity emerged from these studies, generating potentially useful guidelines predicting response design therapies overcoming resistance. In this Review, we will discuss recent put them context with classic views aiming stimulate development therapeutic strategies overcome improve

Язык: Английский

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Long non-coding RNAs in drug resistance across the top five cancers: Update on their roles and mechanisms

Heliyon, Год журнала: 2024, Номер 10(5), С. e27207 - e27207

Опубликована: Март 1, 2024

Cancer drug resistance stands as a formidable obstacle in the relentless fight against top five prevalent cancers: breast, lung, colorectal, prostate, and gastric cancers. These malignancies collectively account for significant portion of cancer-related deaths worldwide. In recent years, long non-coding RNAs (lncRNAs) have emerged pivotal players intricate landscape cancer biology, their roles driving are steadily coming to light. This comprehensive review seeks underscore paramount significance lncRNAs orchestrating across spectrum different drugs, including platinum drugs (DDP), tamoxifen, trastuzumab, 5-fluorouracil (5-FU), paclitaxel (PTX), Androgen Deprivation Therapy (ADT) most types cancer. It delves into multifaceted mechanisms through which exert influence on resistance, shedding light regulatory various facets biology. A understanding these lncRNA-mediated may pave way more effective personalized treatment strategies, ultimately improving patient outcomes challenging malignancies.

Язык: Английский

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Olaparib research update: mechanism, structure and clinical trials

Medicinal Chemistry Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 26, 2025

Язык: Английский

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Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma

Cell Reports, Год журнала: 2023, Номер 42(10), С. 113307 - 113307

Опубликована: Окт. 1, 2023

Ovarian high-grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer with limited therapeutic options and a poor prognosis. In recent years, poly-ADP ribose polymerase (PARP) inhibitors have demonstrated significant clinical benefits, especially in patients BRCA1/2 mutations. However, acquired drug resistance relapse major challenge. Indisulam (E7070) has been identified as molecular glue that brings together splicing factor RBM39 DCAF15 E3 ubiquitin ligase resulting polyubiquitination, degradation, subsequent RNA defects. this work, we demonstrate loss induces defects key DNA damage repair genes cancer, leading to increased sensitivity cisplatin various PARP inhibitors. The addition indisulam also improved olaparib response mice bearing inhibitor-resistant tumors. These findings combining degraders promising approach improve inhibitor HGSC.

Язык: Английский

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PARP Inhibitors for Prostate Cancer: Tangled up in PROfound and PROpel (and TALAPRO-2) Blues

European Urology, Год журнала: 2023, Номер 84(3), С. 253 - 256

Опубликована: Апрель 20, 2023

Язык: Английский

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Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500)

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(4), С. 2349 - 2368

Опубликована: Фев. 1, 2024

ATR is a key kinase in the DNA-damage response (DDR) that synthetic lethal with several other DDR proteins, making it an attractive target for treatment of genetically selected solid tumors. Herein we describe discovery novel inhibitor guided by pharmacophore model to position hydrogen bond. Optimization was driven potency and selectivity over related mTOR, resulting identification camonsertib (RP-3500) high excellent ADME properties. Preclinical evaluation focused on impact myelosuppression, exploration intermittent dosing schedules allow recovery erythroid compartment mitigate anemia. Camonsertib currently undergoing clinical both as single agent combination talazoparib, olaparib, niraparib, lunresertib, or gemcitabine (NCT04497116, NCT04972110, NCT04855656). A preliminary recommended phase 2 dose monotherapy identified 160 mg QD given 3 days/week.

Язык: Английский

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