Tumor biomarkers for diagnosis, prognosis and targeted therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 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.

Language: Английский

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Targeting mutations in cancer

Journal of Clinical Investigation, Journal Year: 2022, Volume and Issue: 132(8)

Published: April 14, 2022

Targeted therapies have come to play an increasingly important role in cancer therapy over the past two decades. This success has been made possible large part by technological advances sequencing, which greatly advanced our understanding of mutational landscape human and genetic drivers present individual tumors. We are rapidly discovering a growing number mutations that occur targetable pathways, thus tumor testing become component choice appropriate therapies. dramatically transformed treatment outcomes disease prognosis some settings, whereas other oncologic contexts, targeted approaches yet demonstrate considerable clinical efficacy. In this Review, we summarize current knowledge range cancers, including hematologic malignancies solid tumors such as non-small cell lung breast cancer. outline seminal examples druggable targeting modalities address research challenges must be overcome maximize therapeutic benefit.

Language: Английский

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Nanomaterials in tumor immunotherapy: new strategies and challenges

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: June 13, 2023

Abstract Tumor immunotherapy exerts its anti-tumor effects by stimulating and enhancing immune responses of the body. It has become another important modality therapy with significant clinical efficacy advantages compared to chemotherapy, radiotherapy targeted therapy. Although various kinds tumor immunotherapeutic drugs have emerged, challenges faced in delivery these drugs, such as poor permeability low cell uptake rate, had prevented their widespread application. Recently, nanomaterials emerged a means for treatment different diseases due targeting properties, biocompatibility functionalities. Moreover, possess characteristics that overcome defects traditional immunotherapy, large drug loading capacity, precise easy modification, thus leading wide application immunotherapy. There are two main classes novel nanoparticles mentioned this review: organic (polymeric nanomaterials, liposomes lipid nanoparticles) inorganic (non-metallic metallic nanomaterials). Besides, fabrication method nanoparticles, Nanoemulsions, was also introduced. In summary, review article mainly discussed research progress based on past few years offers theoretical basis exploring strategies future.

Language: Английский

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Efficacy of subsequent chemotherapy for patients with BRCA1/2-mutated recurrent epithelial ovarian cancer progressing on olaparib versus placebo maintenance: post-hoc analyses of the SOLO2/ENGOT Ov-21 trial

Annals of Oncology, Journal Year: 2022, Volume and Issue: 33(10), P. 1021 - 1028

Published: June 27, 2022

Language: Английский

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DNA damage response revisited: the p53 family and its regulators provide endless cancer therapy opportunities

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(10), P. 1658 - 1669

Published: Oct. 7, 2022

Abstract Antitumor therapeutic strategies that fundamentally rely on the induction of DNA damage to eradicate and inhibit growth cancer cells are integral approaches therapy. Although DNA-damaging therapies advance battle with cancer, resistance, recurrence following treatment common. Thus, searching for vulnerabilities facilitate action agents by sensitizing is an active research area. Therefore, it crucial decipher detailed molecular events involved in responses (DDRs) cancer. The tumor suppressor p53 at hub DDR. Researchers have identified increasing number genes regulated transcriptional functions been shown be critical direct or indirect mediators cell fate, cycle regulation, repair. Posttranslational modifications (PTMs) primarily orchestrate activity response damage. Many molecules mediating PTMs identified. anticancer potential realized targeting these has through experiments clinical trials sensitize agents. This review briefly acknowledges complexity DDR pathways/networks. We specifically focus regulators, protein kinases, E3/E4 ubiquitin ligases their potential.

Language: Английский

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Small molecule inhibitors targeting the cancers

MedComm, Journal Year: 2022, Volume and Issue: 3(4)

Published: Oct. 13, 2022

Compared with traditional therapies, targeted therapy has merits in selectivity, efficacy, and tolerability. Small molecule inhibitors are one of the primary therapies for cancer. Due to their advantages a wide range targets, convenient medication, ability penetrate into central nervous system, many efforts have been devoted developing more small inhibitors. To date, 88 approved by United States Food Drug Administration treat cancers. Despite remarkable progress, cancer treatment still face obstacles, such as low response rate, short duration response, toxicity, biomarkers, resistance. better promote development targeting cancers, we comprehensively reviewed involved all agents pivotal drug candidates clinical trials arranged signaling pathways classification We discussed lessons learned from these agents, proper strategies overcome resistance arising different mechanisms, combination concerned Through our review, hoped provide insights perspectives research treatment.

Language: Английский

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Radiation-induced tumor immune microenvironments and potential targets for combination therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 19, 2023

As one of the four major means cancer treatment including surgery, radiotherapy (RT), chemotherapy, immunotherapy, RT can be applied to various cancers as both a radical and an adjuvant before or after surgery. Although is important modality for treatment, consequential changes caused by in tumor microenvironment (TME) have not yet been fully elucidated. RT-induced damage cells leads different outcomes, such survival, senescence, death. During RT, alterations signaling pathways result local immune microenvironment. However, some are immunosuppressive transform into phenotypes under specific conditions, leading development radioresistance. Patients who radioresistant respond poorly may experience progression. Given that emergence radioresistance inevitable, new radiosensitization treatments urgently needed. In this review, we discuss irradiated TME regimens describe existing potential molecules could targeted improve therapeutic effects RT. Overall, review highlights possibilities synergistic therapy building on research.

Language: Английский

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A new wave of innovations within the DNA damage response

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 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.

Language: Английский

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Drug resistance in ovarian cancer: from mechanism to clinical trial

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 28, 2024

Abstract Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance bottleneck in ovarian treatment. The increasing use novel drugs clinical practice poses challenges for treatment drug-resistant cancer. Continuing to classify drug according type without understanding underlying mechanisms unsuitable current practice. We reviewed literature regarding various and found that main are as follows: abnormalities transmembrane transport, alterations DNA damage repair, dysregulation cancer-associated signaling pathways, epigenetic modifications. methylation, histone modifications noncoding RNA activity, three key classes modifications, constitute pivotal resistance. One can have multiple mechanisms. Moreover, common chemotherapies targeted may cross (overlapping) MicroRNAs (miRNAs) interfere with thus regulate abovementioned pathways. A subclass miRNAs, “epi-miRNAs”, modulate regulators impact therapeutic responses. Thus, we also regulatory influence miRNAs on summarized recent phase I/II trials based multitude new therapies under evaluation, preliminary results encouraging. This review provides insight into classification facilitate successful resistant

Language: Английский

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STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(1), P. e005627 - e005627

Published: Jan. 1, 2023

Background Poly (ADP-ribose) polymerase (PARP) inhibition (PARPi) has demonstrated potent therapeutic efficacy in patients with BRCA-mutant ovarian cancer. However, acquired resistance to PARPi remains a major challenge the clinic. Methods PARPi-resistant cancer mouse models were generated by long-term treatment of olaparib syngeneic Brca1-deficient tumors. Signal transducer and activator transcription 3 (STAT3)-mediated immunosuppression was investigated vitro co-culture experiments vivo analysis immune cells tumor microenvironment (TME) human Whole genome transcriptome performed assess antitumor immunomodulatory effect STING (stimulator interferon genes) agonists on myeloid TME A agonist used overcome STAT3-mediated patient-derived xenografts Results In this study, we uncover an adaptive mechanism PARP mediated tumor-associated macrophages (TAMs) TME. Markedly increased populations protumor are found BRCA-deficient tumors that rendered both murine patients. Mechanistically, elevates STAT3 signaling pathway cells, which turn promotes polarization TAMs. ablation mitigates increases tumor-infiltrating T inhibition. These findings corroborated patient-derived, BRCA1-mutant Importantly, reshape immunosuppressive reprogramming TME-dependent This is further enhanced addition programmed cell death protein-1 blockade. Conclusions We elucidate rendering enrichment TAMs propelled PARPi-induced activation cells. also provide new strategy

Language: Английский

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