Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: promising strategies to overcoming challenges

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 9, 2024

Resistance to targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) is a significant challenge the treatment of this disease. The mechanisms resistance are multifactorial include molecular target alterations activation alternative pathways, tumor heterogeneity microenvironment change, immune evasion, immunosuppression. Promising strategies for overcoming development combination therapies, understanding better use novel drug targets, identification biomarkers, modulation so on. Ongoing research into new therapeutic approaches hold great promise improving outcomes patients with NSCLC. Here, we summarize diverse driving NSCLC latest potential promising overcome help who suffer from

Language: Английский

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Beyond checkpoint inhibitors: the three generations of immunotherapy

Clinical and Experimental Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 21, 2025

Anti-tumor immunotherapy was rediscovered and rejuvenated in the last two decades with discovery of CTLA-4, PD-1 PD-L1 roles inhibiting immune function tumor evasion anti-tumor response. Following approval first checkpoint inhibitor ipilimumab against CTLA-4 melanoma 2011, there has been a rapid development immunotherapy. Furthermore, additional positive negative molecules among T-cell regulatory systems have identified that to fine tune stimulatory or inhibitory cells modulate their functions (checkpoint modulators). Many strategies are being explored target macrophages, NK-cells, cytotoxic T-cells, fibroblasts, endothelial cells, cytokines involved tolerance microbiome. Similar agents modulators, these newer targets potential synergize other classes immunotherapeutic importantly may overcome resistance immunotherapies. In order better understand mechanism action all major immunotherapy, design clinical trials taking advantage different types use them rationally practice either combination sequence, we propose group immunotherapies into three generations: inhibitors as generation, modulators second while those TME third generation. This review discusses generations oncology, actions, trial results indication, for future designs rational applications.

Language: Английский

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The tumor-intrinsic role of the m ⁶ A reader YTHDF2 in regulating immune evasion

Science Immunology, Journal Year: 2024, Volume and Issue: 9(95)

Published: May 31, 2024

Tumors evade attacks from the immune system through various mechanisms. Here, we identify a component of tumor evasion mediated by YTH domain-containing family protein 2 (YTHDF2), reader that usually destabilizes m

Language: Английский

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Understanding and overcoming resistance to immunotherapy in genitourinary cancers

Cancer Biology & Therapy, Journal Year: 2024, Volume and Issue: 25(1)

Published: April 17, 2024

The introduction of novel immunotherapies has significantly transformed the treatment landscape genitourinary (GU) cancers, even becoming standard care in some settings. One such type immunotherapy, immune checkpoint inhibitors (ICIs) like nivolumab, ipilimumab, pembrolizumab, and atezolizumab play a pivotal role by disturbing signaling pathways that limit system's ability to fight tumor cells. Despite profound impact these treatments, not all tumors are responsive. Recent research efforts have been focused on understanding how cancer cells manage evade response identifying possible mechanisms behind resistance immunotherapy. In response, ICIs being combined with other treatments reduce attack through multiple cellular pathways. Additionally, novel, targeted strategies currently investigated develop innovative methods overcoming failure. This article presents comprehensive overview immunotherapy GU cancers as described literature. It explores studies identified genetic markers, cytokines, proteins may predict or we review current overcome this resistance, which include combination sequential therapies, insights into host profile, new therapies. Various approaches combine chemotherapy, therapy, vaccines, radiation studied an effort more effectively While each therapies shown efficacy clinical trials, deeper underscores potential particularly promising area research. Currently, several agents development, along identification key mediators involved resistance. Further is necessary identify predictors response.

Language: Английский

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Current Technologies and Future Perspectives in Immunotherapy towards a Clinical Oncology Approach

Biomedicines, Journal Year: 2024, Volume and Issue: 12(1), P. 217 - 217

Published: Jan. 18, 2024

Immunotherapy is now established as a potent therapeutic paradigm engendering antitumor immune response against wide range of malignancies and other diseases by modulating the system either through stimulation or suppression components such CD4+ T cells, CD8+ B monocytes, macrophages, dendritic natural killer cells. By targeting several checkpoint inhibitors blockers (e.g., PD-1, PD-L1, PD-L2, CTLA-4, LAG3, TIM-3) expressed on surface monoclonal antibodies polyclonal have been developed already translated clinically. In addition, cell-based, CAR cell therapies also shown to be promising effective immunotherapeutic approaches. particular, therapy has benefited from advancements in CRISPR-Cas9 genome editing technology, allowing generation modified cells with enhanced immunity. However, emerging SARS-CoV-2 infection could hijack patient’s releasing pro-inflammatory interleukins cytokines IL-1β, IL-2, IL-6, IL-10, IFN-γ TNF-α, respectively, which can further promote neutrophil extravasation vasodilation blood vessels. Despite significant development advanced technologies, after certain period treatment, cancer relapses due resistance immunotherapy. Resistance may primary (where tumor do not respond treatment), secondary acquired develop gradually ICIs therapy). this context, review aims address existing technologies mechanisms drugs, explain impact COVID-19 treatment. we will discuss what future implementation these strategies drug resistance. Finally, emphasize practical steps lay groundwork for enlightened policy intervention resource allocation care patients.

Language: Английский

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Current Landscape of Cancer Immunotherapy: Harnessing the Immune Arsenal to Overcome Immune Evasion

Biology, Journal Year: 2024, Volume and Issue: 13(5), P. 307 - 307

Published: April 28, 2024

Cancer immune evasion represents a leading hallmark of cancer, posing significant obstacle to the development successful anticancer therapies. However, landscape cancer treatment has significantly evolved, transitioning into era immunotherapy from conventional methods such as surgical resection, radiotherapy, chemotherapy, and targeted drug therapy. Immunotherapy emerged pivotal component in treatment, harnessing body’s system combat offering improved prognostic outcomes for numerous patients. The remarkable success spurred efforts enhance clinical efficacy existing agents strategies. Several immunotherapeutic approaches have received approval treatments, while others are currently preclinical trials. This review explores recent progress unraveling mechanisms evaluates effectiveness diverse strategies, including vaccines, adoptive cell therapy, antibody-based treatments. It encompasses both established treatments those under investigation, providing comprehensive overview through immunological approaches. Additionally, article emphasizes current developments, limitations, challenges immunotherapy. Furthermore, by integrating analyses resistance exploring combination strategies personalized approaches, it offers valuable insights crucial novel

Language: Английский

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Revolutionizing Cancer Treatment: Recent Advances in Immunotherapy

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 2158 - 2158

Published: Sept. 23, 2024

Cancer immunotherapy has emerged as a transformative approach in oncology, utilizing the body’s immune system to specifically target and destroy malignant cells. This review explores scope impact of various immunotherapeutic strategies, including monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy, checkpoint inhibitors, cytokine therapeutic vaccines. Monoclonal such Rituximab Trastuzumab, have revolutionized treatment paradigms for lymphoma breast cancer by offering targeted interventions that reduce off-target effects. CAR-T therapy presents potentially curative option refractory hematologic malignancies, although challenges remain effectively treating solid tumors. Checkpoint inhibitors redefined management cancers like melanoma lung cancer; however, managing immune-related adverse events ensuring durable responses are critical areas focus. Cytokine continues play vital role modulating response, with advancements engineering improving specificity reducing systemic toxicity. Therapeutic vaccines, particularly mRNA-based represent frontier personalized treatment, aiming generate robust, long-lasting against tumor-specific antigens. Despite these advancements, field faces significant challenges, resistance, tumor heterogeneity, immunosuppressive microenvironment. Future research should address obstacles through emerging technologies, next-generation Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-based gene editing, AI-driven drug discovery. By integrating novel approaches, holds promise more durable, less toxic, highly options, ultimately patient outcomes survival rates.

Language: Английский

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Gut Microbiota–Tumor Microenvironment Interactions: Mechanisms and Clinical Implications for Immune Checkpoint Inhibitor Efficacy in Cancer

Cancer Management and Research, Journal Year: 2025, Volume and Issue: Volume 17, P. 171 - 192

Published: Jan. 1, 2025

Cancer immunotherapy has transformed cancer treatment in recent years, with immune checkpoint inhibitors (ICIs) emerging as a key therapeutic approach. ICIs work by inhibiting the mechanisms that allow tumors to evade detection. Although have shown promising results, especially solid tumors, patient responses vary widely due multiple intrinsic and extrinsic factors within tumor microenvironment. Emerging evidence suggests gut microbiota plays pivotal role modulating at site may even influence outcomes patients receiving ICIs. This review explores complex interactions between microenvironment, examining how these could impact effectiveness of ICI therapy. Furthermore, we discuss dysbiosis, an imbalance composition, contribute resistance ICIs, highlight microbiota-targeted strategies potentially overcome this challenge. Additionally, studies investigating diagnostic potential profiles patients, considering microbial markers might aid early detection stratification By integrating insights from preclinical clinical studies, aim shed light on microbiome modulation adjunct tool, paving way for personalized approaches optimize outcomes.

Language: Английский

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Breaking Barriers: The Promise and Challenges of Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 369 - 369

Published: Feb. 5, 2024

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with pronounced immunogenicity, exhibiting rapid proliferation and immune cell infiltration into the tumor microenvironment. TNBC’s heterogeneity poses challenges to immunological treatments, inducing resistance mechanisms in Therapeutic modalities, including checkpoint inhibitors (ICIs) targeting PD-1, PD-L1, CTLA-4, are explored preclinical clinical trials. Promising results emerge from combining ICIs anti-TGF-β VISTA, hindering TNBC growth. cells employ complex evasion strategies involving interactions stromal cells, suppressing recognition through various cytokines, chemokines, metabolites. The recent focus on unraveling humoral cellular components aims disrupt crosstalk within This review identifies latest mechanisms, exploring potential targets for trials overcome enhance patient survival rates.

Language: Английский

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mRNA vaccines: a new era in vaccine development

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 32(10), P. 1543 - 1564

Published: Jan. 1, 2024

The advent of RNA therapy, particularly through the development mRNA cancer vaccines, has ushered in a new era field oncology. This article provides concise overview key principles, recent advancements, and potential implications vaccines as groundbreaking modality treatment. represent revolutionary approach to combatting by leveraging body's innate immune system. These are designed deliver specific sequences encoding cancer-associated antigens, prompting system recognize mount targeted response against malignant cells. personalized adaptive nature holds immense for addressing heterogeneity tailoring treatments individual patients. Recent breakthroughs exemplified success COVID-19 have accelerated their application platform's versatility allows rapid adaptation vaccine candidates various types, presenting an agile promising avenue therapeutic intervention. Clinical trials demonstrated encouraging results terms safety, immunogenicity, efficacy. Pioneering candidates, such BioNTech's BNT111 Moderna's mRNA-4157, exhibited outcomes targeting melanoma solid tumors, respectively. successes underscore elicit robust durable anti-cancer responses. While great promise, challenges manufacturing complexities cost considerations need be addressed widespread adoption. scalable cost-effective processes, along with ongoing clinical research, will pivotal realizing full vaccines. Overall, cutting-edge that promise transforming As research progresses, refining processes crucial advancing these from mainstream oncology practice, offering hope patients fight cancer.

Language: Английский

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