Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer

Molecular Cancer, Год журнала: 2023, Номер 22(1)

Опубликована: Июль 6, 2023

Abstract Breast cancer is the second leading cause of death for women worldwide. The heterogeneity this disease presents a big challenge in its therapeutic management. However, recent advances molecular biology and immunology enable to develop highly targeted therapies many forms breast cancer. primary objective therapy inhibit specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, different growth factors have emerged as potential targets subtypes. Many drugs are currently undergoing clinical trials, some already received FDA approval monotherapy or combination with other treatment yet achieve promise against triple-negative (TNBC). In aspect, immune has come up promising approach specifically TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, adoptive cell transfer been extensively studied setting cancer, especially approved blockers chemotherapeutic treat several trials ongoing. This review provides an overview developments advancements immunotherapies treatment. successes, challenges, prospects were critically discussed portray their profound prospects.

Язык: Английский

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Tumor biomarkers for diagnosis, prognosis and targeted therapy

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

Опубликована: Май 20, 2024

Abstract Tumor biomarkers, the substances which are produced by tumors or body’s responses to during tumorigenesis and progression, have been demonstrated possess critical encouraging value in screening early diagnosis, prognosis prediction, recurrence detection, therapeutic efficacy monitoring of cancers. Over past decades, continuous progress has made exploring discovering novel, sensitive, specific, accurate tumor significantly promoted personalized medicine improved outcomes cancer patients, especially advances molecular biology technologies developed for detection biomarkers. Herein, we summarize discovery development including history conventional innovative used biomarker classification biomarkers based on tissue origins, application clinical management. In particular, highlight recent advancements biomarker-based anticancer-targeted therapies emerging as breakthroughs promising strategies. We also discuss limitations challenges that need be addressed provide insights perspectives turn into opportunities this field. Collectively, multiple emphasized review may guidance precision medicine, broaden horizons future research directions, expedite patients according their rather than organs origin.

Язык: Английский

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To metabolomics and beyond: a technological portfolio to investigate cancer metabolism

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 22, 2023

Abstract Tumour cells have exquisite flexibility in reprogramming their metabolism order to support tumour initiation, progression, metastasis and resistance therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosynthetic redox status sustain increased energetic demand cells. Over last decades, cancer field has seen an explosion new biochemical technologies giving more tools than ever before navigate this complexity. Within cell or tissue, metabolites constitute direct signature molecular phenotype thus profiling concrete clinical applications oncology. Metabolomics fluxomics, are key technological approaches that mainly revolutionized enabling researchers both qualitative mechanistic model cancer. Furthermore, upgrade from bulk single-cell analysis provided unprecedented opportunity investigate biology at cellular resolution allowing depth quantitative complex heterogenous diseases. More recently, advent functional genomic screening allowed identification pathways, processes, biomarkers novel therapeutic targets concert with other allow patient stratification treatment regimens. This review is intended be guide for metabolism, highlighting current emerging technologies, emphasizing advantages, disadvantages potential leading development innovative anti-cancer

Язык: Английский

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BRCAness, Homologous Recombination Deficiencies, and Synthetic Lethality

Cancer Research, Год журнала: 2023, Номер 83(8), С. 1173 - 1174

Опубликована: Апрель 14, 2023

The concept of "BRCAness" was first described in 2004 to define the situation which a homologous recombination repair (HRR) defect tumor relates and phenocopies BRCA1 or BRCA2 loss-of-function mutations. Soon after discovery synthetic lethality PARP1/2 inhibitors BRCA1- BRCA2-deficient cells, McCabe colleagues extended BRCAness deficiency (HRD) by studying sensitivity cancer cells PARP inhibitors. They genetically revealed that HR-related genes (RAD51, RAD54, DSS1, RPA1), DNA damage signaling (ATR, ATM, CHK1, CHK2, NBS1), Fanconi anemia-related (FANCD2, FANCA, FANCC) conferred Thus, acquire either genetic inactivation BRCA HRD genes. Here, we briefly review how genomic profiling can identify deficiencies current difficulty apply BRCAness/HRD clinic. We also discuss utility evaluating select therapies with (olaparib, rucaparib, niraparib, talazoparib, pamiparib, fuzuloparib), topoisomerase I (TOP1) (irinotecan, topotecan, tumor-targeted TOP1 inhibitors), platinum derivatives (cisplatin carboplatin). See related article colleagues, Cancer Res 2006;66:8109-15.

Язык: Английский

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The DNA Damage Response and Inflammation in Cancer

Cancer Discovery, Год журнала: 2023, Номер 13(7), С. 1521 - 1545

Опубликована: Апрель 7, 2023

Genomic stability in normal cells is crucial to avoid oncogenesis. Accordingly, multiple components of the DNA damage response (DDR) operate as bona fide tumor suppressor proteins by preserving genomic stability, eliciting demise with unrepairable lesions, and engaging cell-extrinsic oncosuppression via immunosurveillance. That said, DDR sig-naling can also favor progression resistance therapy. Indeed, signaling cancer has been consistently linked inhibition tumor-targeting immune responses. Here, we discuss complex interactions between inflammation context oncogenesis, progression, Accumulating preclinical clinical evidence indicates that intimately connected emission immunomodulatory signals malignant cells, part a program preserve organismal homeostasis. DDR-driven inflammation, however, have diametrically opposed effects on immunity. Understanding links may unlock novel immunotherapeutic paradigms treat cancer.

Язык: Английский

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A new wave of innovations within the DNA damage response

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 8, 2023

Genome instability has been identified as one of the enabling hallmarks in cancer. DNA damage response (DDR) network is responsible for maintenance genome integrity cells. As cancer cells frequently carry DDR gene deficiencies or suffer from replicative stress, targeting processes could induce excessive damages (or unrepaired DNA) that eventually lead to cell death. Poly (ADP-ribose) polymerase (PARP) inhibitors have brought impressive benefit patients with breast (BRCA) mutation homologous recombination deficiency (HRD), which proves concept synthetic lethality treatment. Moreover, other two scenarios inhibitor application, replication stress and combination chemo- radio- therapy, are under active clinical exploration. In this review, we revisited progress therapy beyond launched first-generation PARP inhibitors. Next generation PARP1 selective inhibitors, maintain efficacy while mitigating side effects, may diversify application clinic. Albeit unavoidable on-mechanism toxicities, several small molecules checkpoints (gatekeepers) shown great promise preliminary results, warrant further evaluations. addition, repair pathways (caretakers) also preclinical development. With these progresses efforts, envision a new wave innovations within come age.

Язык: Английский

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Fecal microbiota transplantation: current challenges and future landscapes

Clinical Microbiology Reviews, Год журнала: 2024, Номер 37(2)

Опубликована: Май 8, 2024

SUMMARYGiven the importance of gut microbial homeostasis in maintaining health, there has been considerable interest developing innovative therapeutic strategies for restoring microbiota. One such approach, fecal microbiota transplantation (FMT), is main "whole microbiome replacement" strategy and integrated into clinical practice guidelines treating recurrent

Язык: Английский

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The balance of STING signaling orchestrates immunity in cancer

Nature Immunology, Год журнала: 2024, Номер 25(7), С. 1144 - 1157

Опубликована: Июнь 25, 2024

Язык: Английский

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Protein neddylation and its role in health and diseases

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

Опубликована: Апрель 4, 2024

Abstract NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like that covalently attached to a lysine residue of substrate through process known as neddylation, catalyzed by the enzyme cascade, namely activating (E1), conjugating (E2), and ligase (E3). The substrates neddylation are categorized into cullins non-cullin proteins. Neddylation activates CRLs (cullin RING ligases), largest family E3 ligases, whereas alters their stability activity, well subcellular localization. Significantly, pathway and/or many abnormally activated or over-expressed in various human diseases, such metabolic disorders, liver dysfunction, neurodegenerative cancers, among others. Thus, targeting becomes attractive strategy for treatment these diseases. In this review, we first provide general introduction on its biochemical regulation, crystal structures enzymes complex with cullin substrates; then discuss how governs key biological processes via modification substrates. We further review literature data dysregulated several particularly cancer, followed outline current efforts discovery small molecule inhibitors promising therapeutic approach. Finally, few perspectives were proposed extensive future investigations.

Язык: Английский

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Schiff bases and their metal complexes to target and overcome (multidrug) resistance in cancer

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 270, С. 116363 - 116363

Опубликована: Март 29, 2024

Язык: Английский

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