Agosti E, Panciani PP, Lombardi G
… +11 more, Preusser M, Rosa G, Mapelli K, Piazza A, Tognetto D, Gagliano C, Denaro L, Padovan M, Fontanella MM, Zeppieri M, Ius T
Cancer Treat Rev
· 2026 Feb · PMID 41478004
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AIM: This study provides a systematic synthesis of current evidence on targeted therapies for optic pathway gliomas (OPGs), emphasizing their molecular rationale, clinical effectiveness, safety profiles, relevance in bot...AIM: This study provides a systematic synthesis of current evidence on targeted therapies for optic pathway gliomas (OPGs), emphasizing their molecular rationale, clinical effectiveness, safety profiles, relevance in both Neurofibromatosis type 1 (NF1) -associated and sporadic cases. METHODS: A systematic literature review was conducted in accordance with PRISMA guidelines using PubMed, Web of Science, and Scopus databases up to April 2025. Eligible studies focused on systemic targeted therapies for OPGs, evaluating efficacy, molecular targets, and adverse events. Both preclinical and clinical data were included, with study quality assessed using the Newcastle-Ottawa Scale. RESULTS: Of 414 records screened, 13 studies (11 clinical and 2 preclinical) met inclusion criteria. Targeted agents included MEK inhibitors, mTOR inhibitors, anti-VEGF agents, and BRAF inhibitors. MEK inhibitors showed promising progression-free survival outcomes, particularly in NF1-associated OPGs, while anti-VEGF therapies rapidly improved visual symptoms in select cases. MEK inhibitors showed the most consistent progression-free survival benefits, particularly in NF1-associated OPGs, with selumetinib emerging as the leading agent with favorable efficacy and safety profiles. These findings support the growing role of biomarker-driven targeted strategies while underscoring unresolved challenges related to long-term safety and optimal treatment duration. CONCLUSION: Targeted therapies constitute a potentially paradigm-shifting development in the management of OPGs, enhancing disease control while improving the prospects for long-term visual preservation. This review underscores the need for individualized, biomarker-driven approaches and highlights challenges including resistance, long-term safety, and therapy duration.
Spiró Z, El-Heliebi A, Mair MJ
… +7 more, Pieber TR, Prietl B, Spiegl-Kreinecker S, Stanzer S, Wöhrer A, Preusser M, Berghoff AS
Cancer Treat Rev
· 2026 Feb · PMID 41475298
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The advent of mutation-informed targeted therapies has transformed medical oncology, delivering durable responses in several cancer types. However, this success has not been universal. Tumors such as glioblastoma have la...The advent of mutation-informed targeted therapies has transformed medical oncology, delivering durable responses in several cancer types. However, this success has not been universal. Tumors such as glioblastoma have largely remained unresponsive to genomics-guided personalized treatments, and in many cancers, the correlation between genetic alterations and therapeutic response remains inconsistent. To address these limitations, functional precision oncology - based on ex vivo drug screening using patient-derived tumor cells - has emerged as a compelling complementary approach. By directly testing drug responses in tumor cells, this strategy seeks to bypass the shortcomings of purely genomic prediction models, particularly in malignancies that have proven refractory to current targeted approaches. This review outlines the state-of-the-art methodologies for patient-derived cell-based drug screening, examining their application across various tumor types and highlighting the current challenges and opportunities in implementing functional precision medicine in clinical oncology.
Ambrosino FA, Pisano C, Napoli MD
… +15 more, Ventriglia J, Tambaro R, Rossetti S, Passarelli A, Cavalcanti E, Cecio R, Fiore F, Setola SV, Troiani T, Lobianco L, Perri E, Lamia M, Calvanese G, Pignata S, Cecere SC
Cancer Treat Rev
· 2026 Feb · PMID 41455155
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Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate, primarily because 75% of patients are diagnosed with advanced FIGO stage III-IV disease. About 50% of patients are now t...Ovarian cancer is the gynecological cancer with the worst prognosis and the highest mortality rate, primarily because 75% of patients are diagnosed with advanced FIGO stage III-IV disease. About 50% of patients are now treated with neoadjuvant chemotherapy followed by interval debulking surgery. In that context, there is a need for accurate predictors of tumor primary chemosensitivity, as it may impact the feasibility of subsequent interval debulking surgery. The cancer antigen 125 ELIMination rate constant K (KELIM) score, a modeled kinetic parameter, is a potential marker of tumor chemosensitivity in patients with ovarian cancer treated with adjuvant or neoadjuvant chemotherapy before interval debulking surgery. This review aims to provide a comprehensive overview of potential predictive factors for response to platinum therapy, focusing on the KELIM score, a marker increasingly used in clinical practice.
van Zwol-Janssens C, van M Rosmalen M, Laven JSE
… +9 more, Nasserinejad K, Visser JA, Anderson RA, Ben-Aharon I, Freour T, Ruddy KJ, Su HI, Louwers YV, Jager A
Cancer Treat Rev
· 2026 Jan · PMID 41447777
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BACKGROUND: In premenopausal women with breast cancer, chemotherapy often leads to amenorrhea that could be temporary or permanent. Anti-Müllerian hormone (AMH) is a potential biomarker predicting resumption of ovarian f...BACKGROUND: In premenopausal women with breast cancer, chemotherapy often leads to amenorrhea that could be temporary or permanent. Anti-Müllerian hormone (AMH) is a potential biomarker predicting resumption of ovarian function, an outcome that aids in the decision making for endocrine therapy. This study aimed to determine the predictive value of pre-chemotherapy AMH levels for resumption of ovarian function. METHODS: We conducted a systematic review and individual patient data (IPD) meta-analysis. Online databases were searched using terms including: AMH, prediction, menses, menses recovery, amenorrhea, chemotherapy-related amenorrhea, anovulation, menopause, infertility, ovarian reserve, premenopausal, breast cancer, chemotherapy. The study protocol was registered with PROSPERO (CRD42021233966). RESULTS: The systematic review included 31 studies, with 26 contributing to the meta-analysis. Eleven studies provided IPD from 1,029 women. Ovarian function resumption rates varied from 24 % to 61 % depending on follow-up time. Pre-chemotherapy AMH was significantly higher in women whose ovarian function resumed, standardized mean difference 0.94 (95 % CI 0.65-1.22) and showed good predictive ability for resumption of ovarian function (AUC 0.79-0.83). However, the identified cut-off values for pre-chemotherapy AMH gave high false negative rates and differed a lot between studies which was much determined by follow-up time, age and used AMH assay. CONCLUSION: Pre-chemotherapy AMH shows association with ovarian function resumption, but a clinically reliable cut-off across assays could not be established using individual patient data. Therefore, due to high inter-assay variability, AMH is not suitable for optimizing endocrine therapy in premenopausal breast cancer patients at this time. Standardizing AMH assays can help in further research into a cut-off value.
Ventelou L, Ginzac A, Ferreira MC
… +5 more, Canetti L, Philippe S, Pinard C, Durando X, Bernadach M
Cancer Treat Rev
· 2026 Jan · PMID 41435530
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BACKGROUND: In 60 % of cases, head and neck cancers (HNCs) are diagnosed at an advanced stage and therefore have a poor prognosis with survival rates of only 49 months. Circulating tumour DNA (ctDNA) has emerged as a min...BACKGROUND: In 60 % of cases, head and neck cancers (HNCs) are diagnosed at an advanced stage and therefore have a poor prognosis with survival rates of only 49 months. Circulating tumour DNA (ctDNA) has emerged as a minimally invasive biomarker able to improve early detection, assess minimal residual disease, monitor systemic treatment response and identify therapeutic targets. This literature review aims to critically synthesise evidence from the past decade on the clinical use of ctDNA in both HPV-related and HPV-unrelated HNCs. PATIENTS AND METHODS: A literature review was performed using PubMed and Cochrane Library on March 11th 2024, updated on November 21st, 2025, using the keywords: "circulating tumour DNA", "head and neck cancer", "ctHPV-DNA associated with HNSCC", "liquid biopsy and HNSCC". RESULTS: After evaluation of 363 articles identified, 92 were included. ctDNA has been investigated for screening, diagnosis, prognostic stratification, treatment-response assessment, relapse detection and identification of therapeutic targets. However, performance varies considerably across studies due to methodological and biological heterogeneity. CONCLUSION: ctDNA shows strong potential for response assessment and post-treatment monitoring, particularly in HPV-related disease. Nevertheless, its integration into clinical practice requires methodological standardisation and validation in larger prospective studies.
Hoo YY, Sia WW, Jaya-Prakason S
… +5 more, Koczwara B, Kong YC, Salem JE, Dechartres A, Bhoo-Pathy N
Cancer Treat Rev
· 2026 Jan · PMID 41422771
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BACKGROUND: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) improve survival in HR+/HER2- breast cancer, but agent-specific cardiotoxicity remains a concern. We evaluated the risk of QTc prolongation, and other cardiova...BACKGROUND: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) improve survival in HR+/HER2- breast cancer, but agent-specific cardiotoxicity remains a concern. We evaluated the risk of QTc prolongation, and other cardiovascular adverse events (CVAEs) associated with ribociclib, palbociclib, and abemaciclib. METHOD: We conducted a systematic review and meta-analysis (up to May 31st, 2025), assessing QTc prolongation and other CVAEs in patients with HR+/HER2- breast cancer receiving CDK4/6i plus endocrine therapy versus endocrine therapy alone. (PROSPERO: CRD42023460559; UICC Technical Fellowship (TF-20-716796). RESULTS: Twenty-three studies (22 RCTs, 1 cohort) were included. CDK4/6i increased the risk of grade 3/4 QTc prolongation (RR 1.83, 95% CI 1.23-2.74), driven by ribociclib (RR 1.95, 95% CI 1.27-2.98). Palbociclib showed no association, whereas no abemaciclib trials reported QTc data. VTE risk was elevated overall (RR 2.57, 95% CI 1.53-4.32), highest with abemaciclib (RR 5.14, 95% CI 3.09-8.54), while palbociclib was borderline (RR 2.13, 95% CI 0.99-4.57). Subgroup analyses revealed no consistent effect modifiers for ribociclib (QTc) or abemaciclib (VTE). No significant increase was observed for other composite CVAEs (RR 0.99, 95% CI 0.83-1.19) or for individual CVAEs. A hypothesis-generating signal for supraventricular arrhythmias was noted with abemaciclib (RR 3.87, 95% CI 1.19-12.53), based on sparse events. Heterogeneity was low across analyses. CONCLUSION: Our findings mandate drug-tailored rather than class-wide cardiovascular monitoring in patients receiving CDK4/6i: ribociclib warrants routine ECG surveillance, abemaciclib requires intensified monitoring for VTE, and palbociclib shows no consistent signal but still merits vigilance.
Camblor DG, Martínez-Castedo B, Martín-Arana J
… +16 more, Gimeno-Valiente F, García-Micó B, Martínez-Picó F, Seguí V, García-Bartolomé M, González D, Guimera A, Huerta M, Roselló S, Gambardella V, Roda D, Pappas L, Parikh A, Carbonell-Asins JA, Cervantes A, Tarazona N
Cancer Treat Rev
· 2026 Jan · PMID 41401645
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In patients with early-stage colorectal cancer (CRC), circulating tumor DNA (ctDNA) testing is increasingly used to detect minimal residual disease (MRD) after curative-intent surgery. This information can guide decision...In patients with early-stage colorectal cancer (CRC), circulating tumor DNA (ctDNA) testing is increasingly used to detect minimal residual disease (MRD) after curative-intent surgery. This information can guide decisions on adjuvant chemotherapy and surveillance. Two main approaches exist, tumor-informed (TI) and tumor-agnostic (TA), however, their diagnostic accuracy in clinical practice remains unclear. We conducted a bivariate diagnostic meta-analysis to compare sensitivity and specificity of TI versus TA ctDNA assays for detecting recurrence in patients with resected CRC. Subgroup analyses were performed based on landmark versus serial sampling strategies. In the serial-sampling setting, TI assays demonstrated markedly higher sensitivity than TA assays (0.88 vs. 0.59; p = 0.001), with no significant differences in false-positive rates. The landmark analyses did not show statistically significant differences between approaches. The results underscore the importance of sampling strategy when selecting a ctDNA test. When longitudinal monitoring is feasible, TI assays provide the most reliable detection of recurrence. This meta-analysis supports tailoring ctDNA testing to the clinical context, prioritizing TI approaches for serial surveillance to better guide adjuvant decision-making and improve patient outcomes.
de Almeida LFC, Leite LF, Cappellaro AP
… +6 more, da Conceição LD, Noronha MM, da Silva JL, de Melo AC, Batalini F, Tarantino P
Cancer Treat Rev
· 2026 Jan · PMID 41401644
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BACKGROUND: Antibody-drug conjugates (ADCs) have redefined the treatment landscape of metastatic breast cancer (mBC), offering durable responses across all subtypes. As multiple ADCs with similar payloads become availabl...BACKGROUND: Antibody-drug conjugates (ADCs) have redefined the treatment landscape of metastatic breast cancer (mBC), offering durable responses across all subtypes. As multiple ADCs with similar payloads become available for the same patient over the course of the disease, determining the optimal sequencing strategy has become an urgent need, particularly given concerns about cross-resistance and reduced efficacy. METHODS: A literature search identified 1868 citations, of which 23 studies (n = 2934 patients) met the inclusion criteria, encompassing ten full-text publications and 13 abstracts. Data on clinical subtypes, sequencing strategies, efficacy outcomes, and real-world evidence (RWE) were extracted and analyzed. RESULTS: In HER2-low mBC, initial ADC exposure produced higher response rates and longer PFS than subsequent ADCs, with median PFS declining from 5.1-7.6 months to 2.1-3.1 months and OS from 16.5-22.8 months to 5.6-8.0 months. In HER2-positive disease, clinical activity was partially preserved with the second ADC, particularly when T-DXd followed T-DM1, with sustained PFS. TNBC and HR+/HER2- cohorts showed a consistent decline in efficacy with second ADC exposure (PFS 2.5-3.1 months). Evidence indicates that switching ADC payloads mitigates cross-resistance, with improved ORR and PFS2 compared to same-payload sequences. Bridging chemotherapy between ADCs did not compromise efficacy and, in some cohorts, yielded a longer PFS than direct sequencing with another ADC with the same payload. CONCLUSION: Emerging evidence indicates that sequential ADC use can be effective despite some cross-resistance, especially when distinct payload mechanisms are employed. Clinical use should consider payload type, timing, and breast cancer subtype, but toxicities remain critical for decision-making. Research providing insights into resistance mechanisms and biomarkers is needed for personalized approaches.
Petrelli F, Trevisan F, Bruschieri L
… +6 more, Riboldi V, Vavassori I, Seghezzi S, Esposito A, Dottorini L, Stefani A
Cancer Treat Rev
· 2026 Jan · PMID 41391209
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BACKGROUND: The management of metastatic prostate cancer (mPC) has shifted from a purely systemic approach to an integrated paradigm incorporating local and metastasis-directed therapies. Advances in imaging and improved...BACKGROUND: The management of metastatic prostate cancer (mPC) has shifted from a purely systemic approach to an integrated paradigm incorporating local and metastasis-directed therapies. Advances in imaging and improved characterization of the oligometastatic state have stimulated renewed interest in aggressive multimodal treatment strategies. OBJECTIVE: To systematically evaluate and grade the evidence from published meta-analyses investigating the efficacy, safety, and credibility of local and metastasis-directed treatments in metastatic or oligometastatic prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This umbrella review followed PRISMA 2020 recommendations and Ioannidis umbrella-review methodology. PubMed, Embase, Web of Science, and Cochrane Library were searched through June 2025. Eligible studies were systematic reviews or meta-analyses with quantitative pooling of outcomes for local treatment (LT; prostate radiotherapy [RT] or radical prostatectomy [RP]), cytoreductive radical prostatectomy (CRP), or metastasis-directed therapy (MDT) using stereotactic body radiotherapy (SBRT). Twenty-one meta-analyses published between 2018 and 2025, enrolling > 160 000 patients, were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoints were overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). Secondary endpoints included local control, toxicity, and prevention of symptomatic pelvic events. When multiple meta-analyses assessed the same association, second-level pooling was performed. Evidence credibility was graded as strong, highly suggestive, suggestive, or weak. RESULTS AND LIMITATIONS: Prostate RT improved OS in low-volume metastatic hormone-sensitive disease (pooled HR ≈ 0.64-0.73) with minimal grade ≥ 3 toxicity (∼5%) and low heterogeneity (I ≈ 0 %). CRP demonstrated suggestive OS and CSS advantages (HR/OR ≈ 0.6-0.8; CSS ≈ 0.5) versus systemic therapy alone but no superiority over RT. MDT/SBRT significantly prolonged PFS (HR ≈ 0.48) and showed emerging OS benefit (HR ≈ 0.60) across randomized trials, with very low rates of serious toxicity (<2%). Local therapy halved the risk of symptomatic pelvic complications (RR 0.50). Limitations include residual heterogeneity in imaging, disease definitions, and non-randomized data for surgical outcomes. CONCLUSIONS: Across 21 meta-analyses, prostate RT provides highly suggestive evidence of survival benefit in low-volume mHSPC, CRP offers suggestive survival improvement in selected patients, and MDT/SBRT achieves highly suggestive evidence for progression control with emerging OS benefit. These strategies represent validated, evidence-based components of modern multimodal mPC management.
Cancer Treat Rev
· 2026 Jan · PMID 41385991
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Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) have emerged as a standard of care for hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, significantly i...Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (CDK4/6i) have emerged as a standard of care for hormone receptor-positive (HR + ), human epidermal growth factor receptor 2-negative (HER2-) breast cancer, significantly improving patient survival. While generally well-tolerated, their use is associated with a spectrum of adverse events, particularly impacting renal, cardiovascular, and metabolic systems. Clinical data indicate a higher incidence of nephrotoxic adverse reactions in patients receiving CDK4/6i compared to control groups, with abemaciclib showing the highest risk ratio. These renal effects can manifest as true acute kidney injury (AKI), including rare cases of acute tubular injury and acute interstitial nephritis, or as a more common "pseudo-AKI." The latter is characterized by an increase in serum creatinine due to the inhibition of renal organic cation transporters (OCT2/MATE), often without an actual decline in glomerular filtration rate (GFR). This highlights the importance of utilizing cystatin C alongside creatinine for accurate GFR assessment. Preclinical studies suggest a complex effect on renal health; while some data indicate acute nephroprotection, long-term rodent models treated with palbociclib after ischemic AKI demonstrated impaired recovery, increased renal fibrosis, and cellular senescence, indicating potentially detrimental long-term chronic effects. Beyond renal considerations, CDK4/6i are also associated with hypertension and electrolyte imbalance like hypokalemia and hyponatremia. Furthermore, these agents are susceptible to significant drug-drug interactions, particularly with CYP3A4 inhibitors/inducers and immunosuppressants, necessitating careful dose adjustments and monitoring, especially in solid organ transplant recipients. This review consolidates current evidence regarding the renal of CDK4/6i, emphasizing the need for vigilant monitoring and a multidisciplinary approach to optimize patient outcomes.
Escudero A, Bellet M, Saura C
… +18 more, Aguilera A, Papakonstantinou A, Tolosa P, García-Sáenz JÁ, Moreno F, López de Sá A, Schettini F, Seguí E, Gonzalez-Rodriguez M, Navarro V, Ferrero-Cafiero JM, González X, Hernando C, Matikas A, Prat A, Oliveira M, Pascual T, Villacampa G
Cancer Treat Rev
· 2026 Jan · PMID 41385990
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BACKGROUND: Several endocrine-based strategies have been evaluated following CDK4/6 inhibition (CDK4/6i) in hormone receptor-positive advanced breast cancer. However, the absence of head-to-head comparisons leave uncerta...BACKGROUND: Several endocrine-based strategies have been evaluated following CDK4/6 inhibition (CDK4/6i) in hormone receptor-positive advanced breast cancer. However, the absence of head-to-head comparisons leave uncertainty regarding the optimal treatment selection. METHODS: A systematic literature search was performed to identify randomized controlled trials (RCTs) evaluating endocrine-based strategies after CDK4/6i for hormone receptor-positive advanced breast cancer. A network meta-analysis was used to compare overall treatment strategies, rather than individual treatments. In addition, an extracted individual patient data meta-analysis was conducted. The primary endpoint was progression-free survival (PFS) evaluated independently in tumors with PI3K-AKT-PTEN alterations, ESR1-mutated and wild-type tumors. RESULTS: A total of 20 RCTs including 4,716 patients were included. In ESR1-mutated tumors, oral SERD/SERM/PROTAC showed numerically better PFS compared with switching CDK4/6i plus fulvestrant (HR = 0.67, 95 % CI 0.45-1.00). In this population, the addition of i) CDK4/6i or ii) mTORi to oral SERDs improved PFS compared with oral SERD/SERM/PROTAC alone (HR = 0.44, 95 % CI 0.27-0.72 and HR = 0.45, 95 % CI 0.23-0.89, respectively). In PI3K-AKT-PTEN altered tumors, the greatest benefit was observed with PI3K/AKT/mTORi plus fulvestrant and oral SERDs plus CDK4/6i (P-scores > 0.75). In ESR1 and PI3K/AKT/PTEN wild-type tumors, several treatment combinations outperformed fulvestrant. The use of PI3K/AKT/mTORi plus fulvestrant was associated with the highest incidence of grade ≥ 3 adverse events (66.0 %). CONCLUSION: This meta-analysis reinforces the importance of molecular stratification in treatment decisions after CDK4/6i progression, highlighting the need for efficacy and safety assessments across biomarker-selected subgroups.
Lin C, Hadfield MJ, Rathore A
… +11 more, Pinho-Schwermann M, Zhang S, Lu S, Hollander PD, Mani SA, Seyhan AA, Santopietro A, Mega A, Cheng L, El-Deiry WS, Carneiro BA
Cancer Treat Rev
· 2026 Jan · PMID 41330005
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Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality. Despite the efficacy of androgen deprivation therapy (ADT), patients with advanced PCa eventually progress to a lethal castration-resist...Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality. Despite the efficacy of androgen deprivation therapy (ADT), patients with advanced PCa eventually progress to a lethal castration-resistant disease state. Cellular senescence represents a stable growth arrest induced by stress signaling cascades or cancer therapeutics, and escape from a senescent state may be implicated in the development of castration resistance. We discuss the mechanisms promoting cellular senescence in PCa and its contribution to therapeutic resistance to ADT, PARP inhibitors, chemotherapy, and radiation. We also summarize the potential of senolytic and senomorphic therapies in targeting senescent prostate cancer cells in the setting of therapy-induced senescence.
Minuti G, Pasqualini G, Avancini A
… +14 more, Giaj-Levra N, Colonese F, Federico AD, Fozza A, Montrone M, Olmetto E, Pastorello E, Reale ML, Riva ST, Roca E, Sini C, Viscardi G, Pilotto S, Passiglia F
Cancer Treat Rev
· 2026 Jan · PMID 41273991
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Bone metastases (BoMs) are a frequent complication in advanced non-small-cell lung cancer (NSCLC), affecting approximately one third of patients at diagnosis and 35-60 % during the disease course. BoMs increase the risk...Bone metastases (BoMs) are a frequent complication in advanced non-small-cell lung cancer (NSCLC), affecting approximately one third of patients at diagnosis and 35-60 % during the disease course. BoMs increase the risk of skeletal-related events (SREs), which have a detrimental impact on prognosis, performance status, and quality of life (QoL). Management of BoMs in NSCLC requires a multimodal approach. Although systemic anti-cancer therapies remain the cornerstone, the optimal management of BoMs in NSCLC also encompasses bone-targeted agents (BTAs) such as bisphosphonates and denosumab, local treatments including radiotherapy and surgical interventions, and supportive care strategies aimed at preventing SREs, alleviating pain, preserving mobility, and maintaining QoL. This review provides an updated overview of best practices for managing BoMs in NSCLC, covering diagnostic work‑up, therapeutic strategies, and the growing role of multidisciplinary care. It emphasizes the importance of supportive interventions, including nutrition and physical activity, to optimize outcomes in the era of targeted and immune-based therapies, alongside comprehensive simultaneous care.
Miliziano D, Sciortino C, Manglaviti S
… +8 more, Ganzinelli M, Lopez-Gutierrez A, Occhipinti M, Proto C, De Braud F, Besse B, Russo GL, Remon J
Cancer Treat Rev
· 2025 Dec · PMID 41259926
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Thymic epithelial tumors (TETs) are rare thoracic malignancies for which surgical resection remains the mainstay treatment, even in advanced stages. For patients with metastatic disease, platinum-based chemotherapy repre...Thymic epithelial tumors (TETs) are rare thoracic malignancies for which surgical resection remains the mainstay treatment, even in advanced stages. For patients with metastatic disease, platinum-based chemotherapy represents the current standard of care in the first-line, with no standard treatment at progression. Much preclinical evidence supports a potential role of angiogenesis in the pathogenesis and progression of TETs. This biological rationale has led to assess the efficacy of several antiangiogenic agents, either in monotherapy or in combination in pre-treated metastatic TET, reporting a clinical meaningful outcome. Despite this efficacy several challenges remain such as the optimal place of angiogenic agents in the treatment sequence, whether they should be applied as monotherapy or in combination, as well as the potential clinical activity of sequential antiangiogenic agents with different mechanisms of action. In this review, we provide a comprehensive overview of the preclinical and clinical evidence supporting angiogenesis as a therapeutic target in TETs. We also propose potential treatment algorithms based on the current literature, while highlighting the ongoing challenges in defining optimal dosing strategies and treatment sequences in this rare disease.
Xue L, Xu T, Cao G
… +28 more, Chen X, Fang M, Feng M, Gui L, Han F, Han Y, Hao C, Hu M, Huang W, Ji D, Jiang H, Lin S, Liu L, Liu Z, Lu H, Qu S, Ren G, Song M, Wang P, Wang X, Yang K, Yu A, Zhang J, Zhang S, Zhang X, Zhang Y, Guo Y, Hu C
Cancer Treat Rev
· 2025 Dec · PMID 41253088
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Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has impr...Head and neck squamous cell carcinoma (HNSCC) is the most prevalent type of head and neck cancer; however, treatment outcomes and patient prognosis remain suboptimal. Although the survival of patients with HNSCC has improved with the widespread use of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) and immune checkpoint inhibitors (ICIs), there remains considerable potential for further improvement. Recent studies suggest that the combination of anti-EGFR monoclonal antibodies and ICIs demonstrates promising efficacy and safety, which has been recommended by international guidelines for patients with recurrent or metastatic disease. Nevertheless, the application of this combination therapy remains in the early stages of exploration, and numerous questions concerning its standardized clinical use remain unanswered, including the mechanisms underlying the synergistic effects of individual agents, therapeutic value across different patient populations, and safety considerations. The Expert Committee of Head and Neck Cancer of the Chinese Society of Clinical Oncology (CSCO) organized an expert panel to develop this expert consensus on the combination of anti-EGFR mAbs and ICIs in the treatment of HNSCC through multiple rounds of discussion based on evidence-based medicine and clinical practice experience. This consensus provides guidance on the mechanisms of treatment with anti-EGFR mAbs plus ICIs, stratified treatment approaches, applications in special populations, and safety management. It is hoped that this consensus will provide clearer and more practical guidance for clinicians, promote the rational application of this combination therapy in clinical practice, and offer more treatment options for patients with HNSCC.
Cancer Treat Rev
· 2025 Dec · PMID 41242178
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PURPOSE: Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic...PURPOSE: Urinary cell-free DNA (ucfDNA) offers a noninvasive approach for cancer detection, but its diagnostic utility in non-urothelial cancers remains unclear. We systematically evaluated the diagnostic and prognostic value of ucfDNA for these cancers and compared its performance with other liquid biopsies through network meta-analysis. EXPERIMENTAL DESIGN: We conducted a systematic search of PubMed, Cochrane Library, and other databases for studies from 2010 to 2025 evaluating ucfDNA for diagnosing or predicting prognosis in non-urothelial cancers. Primary outcomes were pooled diagnostic sensitivity and specificity; secondary outcomes included prognostic hazard ratios (HRs). Study quality was assessed using QUADAS-2, and Bayesian hierarchical models were employed for robust estimates. RESULTS: Twenty-eight studies involving 4,423 participants were included. Overall pooled sensitivity was 0.80 (95 % CI, 0.75-0.85) and specificity was 0.96 (95 % CI, 0.88-0.98), with significant heterogeneity (I > 82 %). Subgroup analysis of studies targeting short amplicons (<70 bp) showed improved specificity of 0.98 and substantially reduced heterogeneity (I = 0 % for specificity). Limited post-treatment ucfDNA reduction was a strong predictor of poor prognosis (pooled HR, 2.76; 95 % CI, 1.94-3.91). Exploratory network meta-analysis in non-small cell lung cancer comparing urine, plasma, and sputum showed overlapping confidence intervals, though the limited available data and wide confidence intervals preclude definitive conclusions regarding comparative performance. Mutation-based assays demonstrated significantly higher specificity than methylation-based approaches (99 % vs. 72 %, P < 0.01). CONCLUSIONS: ucfDNA demonstrates high diagnostic specificity for non-urothelial cancers and provides significant prognostic information. Optimizing assays for ultrashort DNA fragments is critical for enhancing performance and reducing variability. These findings support the potential utility of ucfDNA, particularly as a complementary tool alongside established liquid biopsies like plasma cfDNA, to enhance non-invasive cancer diagnosis and monitoring. Its role as a standalone diagnostic requires further validation, and method standardization remains essential for broad implementation. CLINICAL TRIAL REGISTRATION: PROSPERO CRD420251073863.
Cancer Treat Rev
· 2025 Dec · PMID 41237439
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Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy, achieving durable complete remissions in hematologic cancers. Yet its translation to solid tumors like hepatocellular carcinoma (HCC),...Chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy, achieving durable complete remissions in hematologic cancers. Yet its translation to solid tumors like hepatocellular carcinoma (HCC), a leading cause of cancer-related deaths worldwide, faces formidable barriers, including immunosuppressive tumor microenvironments (TMEs), antigen heterogeneity, and risks of on-target/off-tumor toxicity. This review discusses the evolving role of CAR-T therapy in HCC across three domains: (1) foundational concepts in CAR-T design, mechanistic action, and antigen-targeting strategies; (2) breakthroughs from preclinical studies and early-phase clinical trials, such as glypican-3 (GPC3) and alpha-fetoprotein (AFP) directed CAR-T cells that have demonstrated preliminary safety and anti-tumor activity; and (3) innovative strategies to overcome TME-driven resistance, including metabolic reprogramming and stromal modulation. We highlight cutting-edge engineering solutions such as armored CAR-T cells engineered for cytokine support, dual-targeting constructs to mitigate antigen escape, and hypoxia-resistant designs alongside synergistic approaches combining CAR-T with immune checkpoint inhibitors or tyrosine kinase inhibitors. Furthermore, we dissect emerging tactics to disrupt TME immunosuppression. While CAR-T therapy holds promise for redefining HCC management, its success will depend on overcoming biological and logistical barriers through patient-tailored designs and robust translational pipelines. Future directions should prioritize biomarker-driven clinical trials, scalable manufacturing platforms, and integration with existing multimodal HCC therapies to maximize durable responses.
Fazio R, Audisio A, Bregni G
… +11 more, Sur D, Daprà V, Conti C, Abbassi FZ, Benhima N, Assaf I, Lago LD, Papamichael D, Laethem JV, Saad ED, Sclafani F
Cancer Treat Rev
· 2025 Dec · PMID 41218335
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Older adults are underrepresented in clinical trials, and studies specifically focused on older cancer patients are uncommon. By screening PubMed, EMBASE and proceedings from international meetings, we searched for trial...Older adults are underrepresented in clinical trials, and studies specifically focused on older cancer patients are uncommon. By screening PubMed, EMBASE and proceedings from international meetings, we searched for trials testing systemic therapies in solid cancer patients aged ≥70 years. We identified age-unselected trials testing the same intervention in the same setting. The primary objective was to assess the proportion of older-age-selected trials meeting the target accrual. Secondary objectives included the analysis of the use of geriatric assessment (GA) tools and quality of life (QoL) questionnaires, and the comparison between older-age-selected and matching age-unselected trials. We included 313 trials (10.9 % phase I, 78.6 % phase I/II-II, and 10.5 % phase III). 7.7 % were published in 1990-2000, 40.3 % in 2001-2011, and 52.1 % in 2012-2023. Of 234 evaluable trials, 77.8 % enrolled ≥90 % of the required patients. Premature study discontinuation occurred in 50 cases (5.9 % phase I, 14.2 % phase II, 39.4 % phase III). Among 232 evaluable trials, 60.3 % met the primary endpoint (63.7 % phase I/II-II, 35.5 % phase III). GA and QoL analyses were carried out in 28.1 % and 23 % of trials, respectively. Corresponding age-unselected trials were identified for 154 older-age-selected trials. Compared with age-unselected trials, a lower proportion of older-age-selected trials met the target accrual (83.5 % vs 94.8 %, p = 0.035) or the primary endpoint (63.9 % vs 81.5 %, p = 0.022). In conclusion, older-age-selected trials are increasingly performed but rarely include GA and QoL analyses. Effective strategies to meet target accrual should be implemented especially for phase III trials, which suffer from high rates of premature discontinuation.
Wang H, Gao N, Wang L
… +7 more, Yang F, Liu B, Hu X, Zhao Y, Sha R, Li X, Li H
Cancer Treat Rev
· 2025 Dec · PMID 41205554
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EGFR-mutant lung adenocarcinoma (LUAD) that transforms into small-cell lung cancer (SCLC) following targeted therapy represents a clinically significant mechanism of acquired resistance, occurring in approximately 3-14 %...EGFR-mutant lung adenocarcinoma (LUAD) that transforms into small-cell lung cancer (SCLC) following targeted therapy represents a clinically significant mechanism of acquired resistance, occurring in approximately 3-14 % of cases. This transformed variant, referred to as SCLC after transformation (SCLC-AT), follows an aggressive clinical course and carries a poor prognosis. SCLC-AT retains the original EGFR mutation but significantly down-regulates EGFR protein expression, eliminating its dependence on EGFR signaling while simultaneously acquiring a neuroendocrine phenotype. In nearly all cases, bi-allelic inactivation of both TP53 and RB1 is observed. In this overview, we provide a detailed examination of the molecular mechanisms underlying the transition from EGFR-mutant LUAD to SCLC. By integrating two primary biological concepts, clonal evolution and lineage reprogramming, we examine recent advances concerning the original cell or cells involved, as well as the genetic and epigenetic reprogramming and signaling pathway changes. While the transformation to SCLC is currently considered genetically and epigenetically irreversible, preclinical interventions targeting EZH2, AURKA, and DLL3 have shown potential in reversing the neuroendocrine phenotype or improving tumor immunogenicity. Future research should utilize single-cell and spatial multi-omics technologies to develop predictive models that can facilitate the early detection of impending transformation and guide precision therapies, ultimately enhancing patient outcomes.