Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends

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

Опубликована: Авг. 28, 2023

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.

Язык: Английский

---

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

---

Regulatory mechanisms of PD-1/PD-L1 in cancers

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

Опубликована: Май 18, 2024

Abstract Immune evasion contributes to cancer growth and progression. Cancer cells have the ability activate different immune checkpoint pathways that harbor immunosuppressive functions. The programmed death protein 1 (PD-1) cell ligands (PD-Ls) are considered be major molecules. interaction of PD-1 PD-L1 negatively regulates adaptive response mainly by inhibiting activity effector T while enhancing function regulatory (Tregs), largely contributing maintenance homeostasis prevents dysregulated immunity harmful responses. However, exploit PD-1/PD-L1 axis cause escape in development Blockade neutralizing antibodies restores enhances anti-tumor immunity, achieving remarkable success therapy. Therefore, mechanisms cancers attracted an increasing attention. This article aims provide a comprehensive review roles signaling human autoimmune diseases cancers. We summarize all aspects underlying expression cancers, including genetic, epigenetic, post-transcriptional post-translational mechanisms. In addition, we further progress clinical research on antitumor effects targeting alone combination with other therapeutic approaches, providing new strategies for finding tumor markers developing combined approaches.

Язык: Английский

---

Anticancer Drug Discovery Based on Natural Products: From Computational Approaches to Clinical Studies

Biomedicines, Год журнала: 2024, Номер 12(1), С. 201 - 201

Опубликована: Янв. 16, 2024

Globally, malignancies cause one out of six mortalities, which is a serious health problem. Cancer therapy has always been challenging, apart from major advances in immunotherapies, stem cell transplantation, targeted therapies, hormonal precision medicine, and palliative care, traditional therapies such as surgery, radiation therapy, chemotherapy. Natural products are integral to the development innovative anticancer drugs cancer research, offering scientific community possibility exploring novel natural compounds against cancers. The role like Vincristine Vinblastine thoroughly implicated management leukemia Hodgkin’s disease. computational method initial key approach drug discovery, among various approaches. This review investigates synergy between techniques, highlights their significance discovery process. transition experimental validation highlighted through vitro vivo studies, with examples betulinic acid withaferin A. path toward therapeutic applications have demonstrated clinical studies silvestrol artemisinin, preclinical investigations trials. article also addresses challenges limitations potential anti-cancer drugs. Moreover, integration deep learning artificial intelligence methods may be useful for enhancing products.

Язык: Английский

---

Mechanisms of immune checkpoint inhibitors: insights into the regulation of circular RNAS involved in cancer hallmarks

Cell Death and Disease, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 4, 2024

Abstract Current treatment strategies for cancer, especially advanced are limited and unsatisfactory. One of the most substantial advances in cancer therapy, last decades, was discovery a new layer immunotherapy approach, immune checkpoint inhibitors (ICIs), which can specifically activate cells by targeting checkpoints. Immune checkpoints type immunosuppressive molecules expressed on cells, regulate degree activation avoid autoimmune responses. ICIs, such as anti-PD-1/PD-L1 drugs, has shown inspiring efficacy broad applicability across various cancers. Unfortunately, not all patients benefit remarkably from overall response rates to ICIs remain relatively low types. Moreover, primary acquired resistance pose serious challenges clinical application immunotherapy. Thus, deeper understanding molecular biological properties regulatory mechanisms is urgently needed improve options fo r current therapies. Recently, circular RNAs (circRNAs) have attracted increasing attention, only due their involvement aspects hallmarks, but also impact shaping tumor microenvironment. In this review, we systematically summarize status existing roles circRNAs Meanwhile, aim settle issue an evidence-oriented manner that involved hallmarks effects

Язык: Английский

---

Enhancing immunotherapy response in melanoma: myeloid-derived suppressor cells as a therapeutic target

Journal of Clinical Investigation, Год журнала: 2023, Номер 133(13)

Опубликована: Июль 2, 2023

Despite the remarkable success of immune checkpoint inhibitors (ICIs) in melanoma treatment, resistance to them remains a substantial clinical challenge. Myeloid-derived suppressor cells (MDSCs) represent heterogeneous population myeloid that can suppress antitumor responses mediated by T and natural killer promote tumor growth. They are major contributors ICI play crucial role creating an immunosuppressive microenvironment. Therefore, targeting MDSCs is considered promising strategy improve therapeutic efficacy ICIs. This Review describes mechanism MDSC-mediated suppression, preclinical studies on MDSC targeting, potential strategies for inhibiting functions immunotherapy.

Язык: Английский

---

Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications

Experimental & Molecular Medicine, Год журнала: 2024, Номер 56(1), С. 19 - 31

Опубликована: Янв. 4, 2024

Abstract Cancer immunotherapy has revolutionized the approach to cancer treatment of malignant tumors by harnessing body’s immune system selectively target cells. Despite remarkable advances, there are still challenges in achieving successful clinical responses. Recent evidence suggests that cell-derived exosomes modulate generate effective antitumor responses, making them a cutting-edge therapeutic strategy. However, natural limited application due their low drug delivery efficiency and insufficient capacity. Technological advancements have allowed exosome modifications magnify intrinsic functions, load different cargoes, preferentially tumor sites. These engineered exert potent effects great potential for immunotherapy. In this review, we describe ingenious modification strategies attain desired performance. Moreover, systematically summarize tumor-controlling properties innate adaptive immunity. Collectively, review provides comprehensive intuitive guide modified exosome-based approaches, offering valuable enhance optimize

Язык: Английский

---

Reigniting hope in cancer treatment: the promise and pitfalls of IL-2 and IL-2R targeting strategies

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

Опубликована: Июль 29, 2023

Abstract Interleukin-2 (IL-2) and its receptor (IL-2R) are essential in orchestrating immune responses. Their function expression the tumor microenvironment make them attractive targets for immunotherapy, leading to development of IL-2/IL-2R-targeted therapeutic strategies. However, dynamic interplay between IL-2/IL-2R various cells their dual roles promoting activation tolerance presents a complex landscape clinical exploitation. This review discusses pivotal IL-2 IL-2R tumorigenesis, shedding light on potential as diagnostic prognostic markers manipulation cancer. It underlines necessity balance anti-tumor activity with regulatory T-cell expansion evaluates strategies such dose optimization selective targeting enhanced effectiveness. The article explores recent advancements field, including developing genetically engineered variants, combining therapies other cancer treatments, benefits multidimensional approach integrating molecular profiling, immunological analyses, data. concludes that deeper understanding interactions within is crucial realizing full IL-2-based therapies, heralding promise improved outcomes patients.

Язык: Английский

---

Metal‐based smart nanosystems in cancer immunotherapy

Exploration, Год журнала: 2024, Номер 4(6)

Опубликована: Март 22, 2024

Abstract Metals are an emerging topic in cancer immunotherapy that have shown great potential modulating immunity cycle and promoting antitumor by activating the intrinsic immunostimulatory mechanisms which been identified recent years. The main challenge of metal‐assisted lies fact free metals as ion forms easily cleared during circulation, even cause systemic metal toxicity due to off‐target effects. With rapid development nanomedicine, metal‐based smart nanosystems (MSNs) with unique controllable structure become one most promising delivery carriers solve issue, owing their various endogenous/external stimuli‐responsiveness release ions for metalloimmunotherapy. In this review, state‐of‐the‐art research progress metal‐related is comprehensively summarized. First, mainstream MSNs‐assisted will be delineated. immunological effects certain categorization MSNs different characters compositions then provided, followed representative exemplar applications treatment, synergistic combination immunotherapy. Finally, we conclude review a summary remaining challenges associated provide authors' perspective on further advances.

Язык: Английский

---

A systematic framework for understanding the microbiome in human health and disease: from basic principles to clinical translation

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

Опубликована: Сен. 23, 2024

Язык: Английский

---