The advancement of chemotherapy in breast cancer is moving toward personalization rather than abandonment. Chemotherapy will likely remain essential for many patients, but its delivery is becoming mor

The gap

Consensus across the literature

Supporting evidence — 5 representative gaps

• THE ROLE AND THERAPEUTIC STRATEGIES OF PRECURSOR EXHAUSTED CD8-positive T CELLS IN TUMOR IMMUNITY (2026) · doi

  As a key subset within the exhaustion differentiation hierarchy, Tpex combine self-renewal capacity with redifferentiation potential and have emerged as a central entry point for understanding durable responses to tumor immunotherapy. Current evidence indicates that the long-term efficacy of immune checkpoint blockade depends less on functional recovery of terminally exhausted cells than on the abundance, differentiation plasticity, and niche support of Tpex. Accordingly, optimization of tumor immunotherapy is shifting from a narrow emphasis on enhancing effector function to a broader strategy aimed at maintaining, expanding, and efficiently mobilizing the precursor pool. At the same time, the formation and maintenance of Tpex are jointly shaped by transcriptional regulation, metabolic adaptation, epigenetic remodeling, and microenvironmental signals, suggesting that no single universal regulatory switch exists. Future strategies with stronger translational potential should therefore respect differentiation hierarchy and therapeutic timing, and should emphasize systematic combination designs centered on Tpex expansion, niche remodeling, and intervention in resistance-associated pathways, rather than focusing only on reversal of terminal Tex. Overall, research on Tpex is moving tumor immunotherapy beyond short-term effector intensity and toward a broader concern with durability, plasticity, and the tissue ecology of immune responses. Continued advances in spatial multi-omics, lineage tracing, and dynamic clinical monitoring are expected to deepen both mechanistic understanding and translational application of Tpex biology, thereby providing a stronger theoretical foundation for precision immunotherapy. COMPETING INTERESTS The authors have no relevant financial or non-financial interests to disclose. REFERENCES [1] Alsaafeen B H, Ali B R, Elkord E. Resistance mechanisms to immune checkpoint inhibitors: updated insights. Molecular cancer, 2025, 24(1): 20. [2] Wang J, Yan R, Jia D, et al. Reprogramming T cell stemness against cancer. Trends in cancer, 2026, 12(1): 68-79. [3] Yu Y, Yao X, Wang Q, et al. T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026: e20634. Volume 8, Issue 2, Pp 47-55, 2026 54 ShuHua Chen, et al. [4] Lan X, Mi T, Alli S, et al. Antitumor progenitor exhausted CD8(+) T cells are sustained by TCR engagement. Nature immunology, 2024, 25(6): 1046-1058. [5] Tsui C, Kretschmer L, Rapelius S, et al. MYB orchestrates T cell exhaustion and response to checkpoint inhibition. Nature, 2022, 609(7926): 354-360. [6] Gill A L, Wang P H, Lee J, et al. PD-1 blockade increases the self-renewal of stem-like CD8 T cells to compensate for their accelerated differentiation into effectors. Science immunology, 2023, 8(86): eadg0539. [7] Humblin E, Korpas I, Lu J, et al. Sustained CD28 costimulation is required for self-renewal

  Keywords: tpex immunotherapy differentiation cancer exhaustion self renewal tumor immune checkpoint cells wang cell hierarchy potential
• Breast cancer chemotherapy in transition: predictive markers, resistance mechanisms, and new treatment approaches (2026) · doi

  The advancement of chemotherapy in breast cancer is moving toward personalization rather than abandonment. Chemotherapy will likely remain essential for many patients, but its delivery is becoming more selective, adaptive, and biologically integrated. Future progress will depend on refining predictive markers, espe- cially through multimodal approaches that combine genomic alter- ations, immune contexture, molecular subtyping, and dynamic biomarkers such as ctDNA. Better identification of true chemosensitive disease could minimize toxicity in low-benefit populations while enabling rational escalation in high-risk groups. At the same time, overcoming resistance will require moving beyond single-marker thinking. Resistance is rarely explained by one pathway alone; instead, it reflects evolving tumor ecosystems. Integrative profiling before, during, and after treatment may allow clinicians to identify emerging resistant clones and modify therapy accordingly. The neoadjuvant setting remains ideal for this research because it offers serial tissue access and direct assessment of response. Finally, future therapeutic strategies will likely blend chemo- targeted agents, and post- therapy with immunotherapy, neoadjuvant residual disease–directed interventions. Emerging platforms such as antibody-drug conjugates further suggest that

  Keywords: chemotherapy moving likely future disease resistance emerging therapy neoadjuvant advancement breast cancer toward personalization rather
• Advances in Radiotherapy for Soft Tissue Sarcomas in 2025: A Review (2026) · doi

  ● Integration of Biomarkers for Personalized RT: The future lies in moving beyond a one-size-fits-all ap- proach. The integration of histotype-specific response patterns [2], molecular profiles (e.g., CINSARC [42], PARP expression [25]), and real-time response data from mpMRI [23] or circulating tumor DNA will enable truly personalized RT prescriptions. Future trials must stratify patients using these biomarkers to test adaptive dose escalation, de-escalation, or specific combinatorial strategies. ● Next-Generation Systemic-RT Combinations and Sequencing: Building on early successes with PARPi and ICIs, research must optimize the sequencing, tim- ing, and dosing of these combinations. Furthermore, exploring novel agents (e.g., next-generation anti-an- giogenics, bispecific antibodies) and cellular therapies (CAR-T/NK cells) in combination with RT, guided by predictive biomarkers of synergy, represents a fertile frontier [12, 29]. ● AI-Enhanced Adaptive Radiotherapy and Quanti- tative Response Assessment: The fusion of artificial intelligence (AI) with adaptive RT platforms will be transformative. AI algorithms can automate the analy- sis of mpMRI and other imaging data to predict early response, enabling fully dynamic treatment adaptation [22]. Similarly, AI can aid in validating and standardiz- ing novel surrogate endpoints like hyalinization [28] or radiomic signatures, accelerating trial conduct. ● Validation of Surrogate Markers: Surrogate markers such as hyalinization [28], monocyte infiltration [41], and mpMRI parameters [23] need validation in large- scale prospective, multi-institutional trials to potentially replace traditional endpoints (e.g., OS, PFS) in clinical trials. This would accelerate the development of novel RT strategies by reducing trial duration and sample size requirements. ● Standardized QoL Measurement and Value-Based Care: Implementation of standardized QoL tools such as STS-QoL [43] in clinical practice and trials will enable Page 11 of 15 50 consistent monitoring of patient-reported outcomes. Fu- ture research should focus on identifying interventions to mitigate QoL declines during RT (e.g., supportive care, rehabilitation) and correlating QoL with long- term functional outcomes. Integrating patient-reported outcomes into clinical decision-making is essential for value-based oncology care. ● Global Access to Advanced RT Technologies: Ad- dressing disparities in access to hypofractionation, par- ticle therapy, and adaptive RT is critical. Foppele et al. [5] showed that hypofractionation can be implemented in resource-limited settings during the pandemic, and future efforts should focus on expanding access to cost- effective advanced RT technologies worldwide. This includes technology transfer, training, and the develop- ment of simplified yet effective hypofractionated proto- cols suitable for diverse healthcare environments.

  Keywords: response trials adaptive biomarkers future mpmri novel surrogate clinical care outcomes access integration personalized size
• Current advances in immunotherapy for KRAS-Mutant pancreatic cancer (2026) · doi

  Conclusions: This Review systematically elucidates that KRAS mutations in PDAC not only drive autonomous tumor cell proliferation but also orchestrate a profoundly immunosuppressive “cold” TME. This is achieved through multiple, interconnected mechanisms, including induction of immune cell dysfunction and exhaustion, recruitment of immunosuppressive populations such as MDSCs, establishment of a dense fibrotic stromal barrier, and metabolic reprogramming centered on enhanced glycolysis. Collectively, these processes constitute the fundamental basis for the intrinsic resistance of PDAC to immunotherapy. In response to the repeated failure of ICI monotherapy, the current ARTICLE IN PRESSARTICLE IN PRESS ACCEPTED MANUSCRIPT ARTICLE IN PRESS research paradigm has shifted toward multimodal combination strategies. This Review summarizes the major therapeutic avenues under active investigation: combinations of immunotherapy with radiotherapy or chemotherapy leverage the “in situ vaccine” effect of radiotherapy and the immunomodulatory properties of cytotoxic agents to promote immune activation; combinations of immunotherapy with targeted therapies—including direct KRAS G12C/G12D inhibitors, PARP inhibitors, MEK inhibitors, and FAK inhibitors—aim to disrupt oncogenic signaling or cooperative pathways while simultaneously alleviating immune suppression; emerging immunotherapeutic modalities such as CAR-T cell therapy, oncolytic viruses, and CD40 agonists seek to directly activate or reprogram antitumor immune responses; and innovative local drug-delivery systems—including injectable hydrogels, stimuli-responsive nanoparticles, and oral spore-based carriers—provide critical technological support for achieving high intratumoral drug concentrations with prolonged retention and minimal systemic toxicity. Accumulating preclinical and clinical evidence indicates that rational combination strategies capable of systematically remodeling the TME are central to reversing immune tolerance and restoring effective antitumor immunity in PDAC. Future perspectives: Future breakthroughs are likely to arise from a paradigm shift from “broad combination” approaches to “precision synergy.” A primary objective will be the development of predictive biomarker systems through the integration of ctDNA dynamics, spatial transcriptomics, proteomics, and other multi-omics technologies, enabling accurate identification of patient subgroups most likely to benefit from specific combination strategies. Such biomarker-driven stratification will be essential for implementing truly personalized immunotherapy. Building on this foundation, therapeutic strategies must evolve toward “dynamic precision intervention,” involving the development of agents or combinatorial regimens that simultaneously target KRAS signaling, stromal barriers, and metabolic reprogramming. Coupled with intelligent local delivery systems that allow spa

  Keywords: immune immunotherapy combination strategies inhibitors kras pdac cell including article press systems review systematically immunosuppressive
• Breakthrough of solid tumor treatment: CAR-NK immunotherapy (2024) · doi

  Due to the recent proposal of CAR-NK therapy, there are currently very few CAR end designs available for reference, especially for solid tumors. It is unclear whether there is a universal design that is effective for all solid tumors or whether there is a specific optimal solution design for each solid tumor. Moreover, the current experimental sample size is generally too small and lacks integration. We need a large number of basic and clinical trials to verify and compare the effects of various CARs. Further validation is needed to determine whether CAR-NK can be widely applied in the treatment of solid tumors in clinical practice in the future. to survive and grow, INTRODUCTION Under normal circumstances, the immune system can identify and eliminate tumor cells within the Tumor microenvironment (TME). tumor cells employ diverse However, strategies to suppress the immune system, enabling their survival during different stages of the anti-tumor immune response. This phenomenon, where tumor cells exhibit the described character- istics, is termed ‘immune escape’ [1]. Tumor immunotherapy is a treatment method to control and eradicate tumors by combating immune escape and reinstating the body’s normal anti-tumor immune response. Chimeric antigen receptors (CARs) are fusion proteins, and the CAR structure of CAR-NK cells typically comprises three components: the extracellular antigen-binding region (usually scFv), the spacer and the transmembrane domain, and the intracellular activation domain. Natural Killer (NK) cells, as unique innate immune cells, display rapid and potent cytotoxicity for cancer immunotherapy and pathogen clearance without prior sensitization or antigen recognition [2]. CAR-NK cells are engineered to express CAR through genetic modification, connecting antibodies (or receptors) recognizing surface antigens of target cells (e.g. virus infected cells and cancer cells) with Signaling molecule required to activate immune cells. This modification can counteract inhibitory receptors, thereby enhan- cing NK cells’ specific killing effect on target cells [3]. For patients with solid tumor who are clinically advanced or extensively metastasized with poor responses to surgical and 1Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 2Department of Radiotherapy, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. 3Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China. 4Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 5Department of Colorectal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. email: [email protected]; [email protected]; [email protected] ✉ Received: 24 November 2023 Revised: 4 January 2024 Accepted: 9 January 2024 Official journal of CDDpress 2 W. Wang et al. conventi

  Keywords: cells zhengzhou tumor immune hospital cancer solid liated university china tumors department there whether antigen