solid tumors

Overview

Solid tumors are malignant neoplasms that arise in organs or tissues and form a discrete mass, in contrast to hematologic cancers such as leukemia and lymphoma. They include a broad range of cancers, such as colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, ovarian adenocarcinoma, and many others. Biologically, solid tumors are characterized by marked cellular heterogeneity, abnormal tumor vasculature, stromal and fibrotic components, immune suppression, and spatially uneven drug delivery. These features contribute to treatment resistance and make solid tumors more difficult to eradicate with systemic therapy than many blood cancers.

From a therapeutic perspective, solid tumors are a major focus of oncology research because they remain only partially responsive to several advanced modalities, including CAR-T cell therapy, bispecific T-cell engagers, cancer vaccines, and checkpoint inhibitor. Recent work has emphasized the tumor microenvironment, antigen heterogeneity, mechanical barriers to penetration, and circadian and metabolic influences on treatment response. As a result, solid tumors are not a single disease entity but a diverse class of cancers unified by shared challenges in diagnosis, drug delivery, immune evasion, and durable control.

Focus of Latest Publications

Recent publications have examined solid tumors as a target across immunotherapy, nanomedicine, pharmacology, imaging, and translational biomarker studies.

A major theme is the difficulty of applying cell-based immunotherapies to solid tumors. Several studies focused on CAR-T approaches and related immune-engaging strategies. One report described a convergent uPAR-positive tumor ecosystem that creates broad vulnerability to CAR T cell therapy, highlighting that solid tumors remain limited by antigen heterogeneity and a suppressive, pro-fibrotic microenvironment. Another study developed a clickable universal tumor-antigen equipping strategy, termed CUTE, to help remedial CAR-T cells destroy solid tumors by addressing the scarcity of tumor-specific antigens. In a related direction, antigen spreading mediated heterogeneous solid tumor eradication by DNA demethylating agent-programmed CAR T cells, suggesting that decitabine-programmed CAR T cells may broaden recognition of heterogeneous tumor cell populations. Additional work on in vivo CAR therapies noted ongoing clinical trials for solid tumors, reflecting continued efforts to overcome delivery and persistence barriers. A separate study on in vivo tracking of CAR-T cells in tumors via nanobubble-based contrast-enhanced ultrasound underscored the need to monitor CAR-T localization and behavior in solid tumor settings.

Bispecific and trispecific immune engagers were also explored. A 5T4-Vδ2 bispecific T cell engager recruited Vγ9Vδ2-T cells for tumor-selective cytotoxicity across solid malignancies, leveraging the oncofetal antigen 5T4, which is aberrantly expressed in many cancers but sparse in healthy adult tissues. Another report on trispecific antibodies noted encouraging early clinical activity in selected solid tumors, although broader application remains constrained by limited efficacy in this disease class. ARC101, a CLDN6-specific T-cell engager for ovarian adenocarcinoma, was presented as a differentiated bispecific immunotherapy with exceptional tumor selectivity and optimized T-cell activity for solid tumors.

The tumor microenvironment was a recurring target. CART-Vac, an mRNA-LNP vaccine providing antigen and co-stimulation in the tumor microenvironment, was reported to enhance CAR T cell function in solid tumors, suggesting that local immune conditioning can improve therapeutic performance. Long-acting IL-7 induced distinct transcriptomic features in peripheral T cells of patients with solid tumors, indicating systemic immune modulation as another strategy to support antitumor immunity. Proteostasis was also linked to T cell differentiation potential and tumor-infiltrating lymphocyte function, with preserved stem-like TCF1+ populations improving function in tumors. These findings collectively reinforce the importance of T-cell fitness, persistence, and differentiation state in solid tumor immunotherapy.

Several studies addressed the physical and biochemical barriers that limit drug delivery in solid tumors. A unified biochemical-physical regulatory nanoparticle was designed to modulate tumor mechanics and augment nanomedicine penetration, offering a strategy to overcome mechanical barriers in solid tumors. Bio-inspired fractal-structured gel-drugs enabled deep tumor penetration for efficient chemotherapy of hepatocellular carcinoma, again emphasizing the challenge of intratumoral transport. Another study on spatial pharmacometrics noted that spatial heterogeneity in drug distribution within solid tumors compromises target engagement and is rarely represented in population pharmacokinetic analyses. These findings align with the broader recognition that solid tumors often contain poorly perfused, heterogeneous regions that reduce effective drug exposure.

Nanotechnology-based antitumor platforms were prominent. Potent polydopamine-based cascade nanozymes acted as ROS amplifiers for triple photothermal-catalytic-chemotherapy and effectively inhibited tumor development while maintaining biocompatibility. Hypoxia-responsive nanoparticles, gold nanoparticles, and biomaterials were also part of the broader methodological landscape used to improve delivery and local activity in solid tumors. A doxorubicin and lactobionic acid-containing systems were among the chemical and formulation strategies used to improve tumor targeting in related studies. These approaches reflect a common goal: to increase intratumoral accumulation while reducing systemic toxicity.

Metabolic and resistance pathways were investigated in solid tumor models. Artesunate was reported to overcome oxaliplatin resistance in colorectal cancer by inducing ferroptosis through inhibition of the CDK5/Nrf2/GPX4 pathway, with in vivo experiments showing reduced tumor growth and low toxicity in xenograft models. Another study combining network pharmacology and transcriptomics evaluated Shenqiyichang decoction in colorectal cancer, reporting suppression of tumor progression through NQO1 inhibition, ROS activation, and Wnt/β-catenin signaling. A separate report on mTOR inhibition and ATRA-induced differentiation noted that the therapeutic effect was attenuated or absent in solid tumors, underscoring lineage-specific differences in response to differentiation-based therapy.

Imaging and biomarker-guided care were also represented. A novel Fap-targeted PET tracer was developed and piloted for tumor imaging, building on the promise of FAPI tracers for diagnosis. The IMMUNO-BIOMAP trial in NSCLC used an adaptive multimodal framework to longitudinally profile tumors and the microenvironment in order to identify resistance mechanisms in real time. This reflects a broader shift toward dynamic biomarker-guided management of solid tumors rather than static baseline profiling alone.

Clinical and epidemiologic studies extended the scope beyond direct antitumor mechanisms. A nationwide cohort study examined the impact of COVID-19 and vaccination on long-term survival in patients with solid malignancies, addressing how infection and immunization intersect with oncologic outcomes and systemic anticancer therapies. Another study compared the quality of dying and quality of care between patients with hematological malignancies and those with solid tumors, highlighting differences in end-of-life trajectories and care patterns. Differences in end-of-life policies between hematologists and gastroenterologists similarly noted that patients with solid tumors more often transition to end-of-life care than those with hematologic malignancies.

Finally, some studies explored broader biological modifiers of treatment response. A real-world evidence study examined the impact of the circadian clock on benefit from immune checkpoint inhibitors in solid tumors, suggesting that time-of-day-dependent tumor-immune interactions may influence clinical outcomes. Another study on Fap-targeted PET imaging and a report on spatial pharmacometrics both reinforced the importance of tumor architecture and stromal biology in solid tumor research. Together, these publications portray solid tumors as a highly heterogeneous disease class in which immune evasion, stromal barriers, metabolic adaptation, and spatial drug-distribution constraints are central therapeutic challenges.

Key Publications

• Jun Real-world evidence for the impact of circadian clock on the benefit from immune checkpoint inhibitors in solid tumors. (BMC cancer, 2026, PMID 42316066): "The circadian clock regulates tumor-immune interactions in a time-of-day-dependent manner, yet whether this translates to a clinically meaningful benefit across diverse solid tumors in real-world populations remains unclear."
• Jun mRNA-LNP vaccine providing antigen and co-stimulation in the tumor microenvironment enhances CAR T cell function (CART-Vac). (Molecular therapy. Oncology, 2026, PMID 42256207): "These findings suggest that CART-Vac can modulate the TME, offering a promising strategy to improve the therapeutic efficacy of CAR T cells in solid tumors."
• Jun The IMMUNO-BIOMAP trial in NSCLC: An adaptive multimodal framework for biomarker-guided care. (Cell reports. Medicine, 2026, PMID 42302749): "...which longitudinally profile tumors and the microenvironment to identify resistance mechanisms in real time..."
• Mar Combining network pharmacology and transcriptomics to validate and explore Shenqiyichang decoction in treating colorectal cancer by NQO1 inhibition, ROS activation and Wnt/β-catenin signaling pathway. (Journal of ethnopharmacology, 2026, PMID 41786058): "It has been demonstrated to effectively suppress the progression of tumors and enhance patients' quality of life."
• Jun Bio-inspired fractal-structured gel-drugs enable enhancing deep tumor penetration for efficient chemotherapy of hepatocellular carcinoma. (Journal of controlled release : official journal of the Controlled Release Society, 2026, PMID 41932369): "...providing an avenue for deep penetration treatment of solid tumors."
• Jun Partial Differential Equation (PDE)-Based Spatial Pharmacometrics in NONMEM: Method of Lines (MOL) Implementation with AI-Assisted Model Development. (Journal of clinical pharmacology, 2026, PMID 42212532): "Spatial heterogeneity in drug distribution, particularly within solid tumors, compromises target engagement, yet is rarely represented in population pharmacokinetic analyses."
• Jun A trophoblast glycoprotein specific 5T4-Vδ2 bispecific T cell engager recruits Vγ9Vδ2-T cells for tumor-selective cytotoxicity across solid malignancies. (Clinical immunology (Orlando, Fla.), 2026, PMID 41999960): "5T4 is an oncofetal antigen that is aberrantly expressed across a wide range of malignancies, but only sparsely present in healthy adult tissues."
• Jun Transoral endoscopic approach to skull base lesions: A 10-year experience at a single tertiary center. (Neurosurgical review, 2026, PMID 42217086): "A transoral sublabial incision with an endoscopic transmaxillary corridor was used in 33 cases with various lesions, including carcinomas, sarcomas, and benign tumors centered in the infratemporal fossa."
• May Artesunate overcomes oxaliplatin resistance in colorectal cancer by inducing ferroptosis through inhibition of the CDK5/Nrf2/GPX4 pathway. (Apoptosis : an international journal on programmed cell death, 2026, PMID 42178429): "The in vivo experiments exhibited that combination of ART and sh-CDK5 reduce the growth of tumors with low toxicity in xenograft models, and reduced Nrf2 and GPX4 expression."
• May Potent Polydopamine-Based Cascade Nanozyme as ROS Amplifier for Triple Photothermal-Catalytic- Chemotherapy. (Bioconjugate chemistry, 2026, PMID 42043281): "In vitro and in vivo antitumor efficacy studies have revealed that FeDD nanozyme could effectively inhibit the development of tumors while maintaining a high level of biocompatibility."