Cancer Treat. Rev. [JOURNAL]
Sun
200 papers
Progress toward personalized management of stage II/III triple negative breast cancer.
Valle I, Ribeiro JM, Grinda T … +4 more , Kok M, Pistilli B, Werutsky G, Rassy E
Cancer Treat Rev · 2026 Jun · PMID 42068737 · Publisher ↗
Triple negative breast cancer (TNBC) is a biologically heterogeneous disease that is treated according to stage at diagnosis. Early steps toward treatment personalization used staging for prognostication and later incorp...
Triple negative breast cancer (TNBC) is a biologically heterogeneous disease that is treated according to stage at diagnosis. Early steps toward treatment personalization used staging for prognostication and later incorporated residual disease burden after neoadjuvant therapy to guide adjuvant treatment decisions. Therapeutic advances, particularly with immunotherapy and poly (ADP-ribose) polymerase inhibitors, have progressed more rapidly than the ability of clinical trials to adapt accordingly, leaving many critical questions regarding treatment combinations and sequencing unanswered. Adapting neoadjuvant and adjuvant strategies according to dynamic changes in the tumor, tumor microenvironment (TME) and novel biomarkers dynamics offers a compelling framework for both treatments escalation and de-escalatation. This review traces the historical evolution of TNBC treatment, examines the challenges of tumor heterogeneity and residual disease after neoadjuvant therapy, and explores the prognostic impact of the TME. We then appraise the latest evidence on poly (ADP-ribose) polymerase inhibitors, antibody-drug conjugates, and immunotherapy in the early setting, outlining a path toward more individualized therapeutic approaches.
Streptozotocin revisited: Pharmacological determinants supporting new scheduling strategies in neuroendocrine tumours.
Fazio N, Spada F, Benini L … +3 more , Mulargiu C, Del Re M, Danesi R
Cancer Treat Rev · 2026 May · PMID 42061024 · Publisher ↗
Streptozotocin (STZ) remains a potentially effective chemotherapeutic agent for pancreatic neuroendocrine tumours, more than five decades after its initial use. Despite its longstanding clinical application, STZ dosing r...
Streptozotocin (STZ) remains a potentially effective chemotherapeutic agent for pancreatic neuroendocrine tumours, more than five decades after its initial use. Despite its longstanding clinical application, STZ dosing regimens have traditionally been driven by empirical practice rather than by pharmacokinetic or pharmacodynamic rationale. Recent advances in understanding its molecular mechanism of action, selective uptake via the glucose transporter type 2 transporter, and DNA-methylating properties provide a solid foundation for revisiting its therapeutic role and optimising its scheduling. This review outlines the key pharmacological features of STZ, including its rapid systemic clearance, narrow volume of distribution, and renal elimination, all of which support the use of short intravenous infusions and fractionated schedules to minimise nephrotoxicity while maintaining efficacy. Comparative insights with temozolomide highlight the unique delivery and tissue tropism advantages of STZ, particularly in pancreatic neuroendocrine tumours. In addition, emerging biomarkers, such as O⁶-methylguanine-DNA methyltransferase deficiency and mismatch repair status, may help refine patient selection for STZ-based chemotherapy. Clinical data from classical and modern regimens, such as those combining STZ with 5-fluorouracil or capecitabine, suggest sustained disease control in well-selected patients. The potential for biomarker-guided strategies and pharmacology-informed protocols supports a contemporary repositioning of STZ in neuroendocrine oncology. Rational redesign of dosing, improved toxicity management, and integration with personalised medicine may revitalise the clinical utility of this historically valuable agent.
Management of infections in the outpatient care of patients with cancer.
Sandherr M, Maschmeyer G, Rieger C
Cancer Treat Rev · 2026 May · PMID 42061023 · Publisher ↗
Infections are a common complication in immunocompromised patients with haematological and oncological diseases, including in outpatient settings. They lead to distressing morbidity and can delay or jeopardize the implem...
Infections are a common complication in immunocompromised patients with haematological and oncological diseases, including in outpatient settings. They lead to distressing morbidity and can delay or jeopardize the implementation of effective antineoplastic therapy. Identifying risk groups for complicated infections may reduce morbidity and mortality. The prevention of bacterial and viral infections as well as Pneumocystis jirovecii pneumonia through drug prophylaxis and consistent vaccination are essential here. In many cases, precise clinical evaluation of patients with febrile neutropenia allows for outpatient empirical and pre-emptive oral antimicrobial therapy and avoids unnecessary hospital stays. These recommendations are based on guidelines developed by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) for the prophylaxis, diagnosis, and treatment of these patients, which are available on the Onkopedia platform of the DGHO (www.onkopedia.com). The recommendations are backed-up by systematic literature reviews, uniform assessment of the strength of evidence, and a consensus-building process.
Expanding the therapeutic Frontier: Liver transplantation for unresectable colorectal liver metastases.
Munster AB, Mahmood U, Fuller H … +6 more , Seo H, Murphy J, Menon K, Imber C, Bhan C, Khan K
Cancer Treat Rev · 2026 May · PMID 42048786 · Publisher ↗
A substantial proportion of patients with colorectal cancer present with or ultimately develop metastatic disease confined to the liver. The management of colorectal liver metastases remains one of the most complex and d...
A substantial proportion of patients with colorectal cancer present with or ultimately develop metastatic disease confined to the liver. The management of colorectal liver metastases remains one of the most complex and debated areas in oncological practice, with curative resection feasible in only a minority of cases. However, emerging evidence, most notably from the TransMet study, has reshaped the therapeutic landscape. The demonstration of a clear survival advantage in carefully selected patients with unresectable hepatic disease undergoing liver transplantation represents a transformative advance and challenges longstanding treatment paradigms. This narrative review critically appraises the epidemiological burden of colorectal liver metastases and delineates the key biological and clinical determinants underpinning their development. We synthesise the pivotal clinical trial data establishing the rationale for liver transplantation in this population and define the parameters for appropriate patient selection. The evolving perioperative integration of systemic therapies and the optimisation of postoperative surveillance strategies are examined in detail. Finally, we evaluate the emerging role of liquid biopsy as a precision tool to refine risk stratification and guide management, while addressing the ethical, logistical, and immunological considerations inherent to expanding transplant indications in this setting.
Targeting claudins in gastric cancer: A novel GLOWing strategy in the SPOTLIGHT.
Balsa M, Alonso S, Sánchez L … +17 more , Bugés C, Layos L, Calvo M, Garsot E, Viciano M, Clavell A, López R, Uchima H, Muñoz R, Muriel R, González B, Mirallas O, Murphy MB, Terán E, Montal R, Fleitas T, Hierro C
Cancer Treat Rev · 2026 May · PMID 42035746 · Publisher ↗
Gastric cancer is one of the most aggressive and lethal malignancies, with limited reliable biomarkers to inform prognosis and therapeutic decision-making. Claudins, which are tight junction proteins that establish epith...
Gastric cancer is one of the most aggressive and lethal malignancies, with limited reliable biomarkers to inform prognosis and therapeutic decision-making. Claudins, which are tight junction proteins that establish epithelial polarity, have recently emerged as clinically actionable targets. CLDN18.2, typically sequestered within the tight junctions of gastric epithelial cells, becomes accessible during malignant transformation and is currently regarded as a critical standard marker in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. Zolbetuximab, a chimeric IgG1 monoclonal antibody targeting CLDN18.2, has shown a survival advantage when used in conjunction with chemotherapy in phase III trials. In light of this evidence, novel strategies are being investigated, including antibody-drug conjugates (ADC) targeting CLDN18.2, bispecific antibodies (BsAb), and cell therapies such as (CAR-T). In parallel, the oncofetal antigen CLDN6, which is inactive in adult tissues but re-expressed in a subset of tumours, has emerged as an interesting target for the development of new therapeutic strategies under investigation. However, despite the development of new drugs and the approval of zolbetuximab, there are significant challenges to be addressed, such as intratumoural heterogeneity, sampling bias, and the absence of assay standardization with thresholds suitable for the modality. This review synthesizes the biology and clinical significance of claudins-particularly CLDN18.2 and CLDN6-, highlighting their potential as biomarkers for guiding precision medicine and future development of novel therapeutic agents in gastric cancer patients.
Perioperative strategies for resectable EGFR-Mutant NSCLC: evidence hierarchy and clinical decision-making.
Zhao S, Liu X, Wang J … +6 more , Tang B, Long Q, Tang X, Dai J, Jiang Y, Liu Q
Cancer Treat Rev · 2026 May · PMID 42033967 · Publisher ↗
The management of resectable non-small cell lung cancer (NSCLC) with EGFR-sensitizing mutations has changed substantially over the past decade, with adjuvant osimertinib now representing the most mature perioperative str...
The management of resectable non-small cell lung cancer (NSCLC) with EGFR-sensitizing mutations has changed substantially over the past decade, with adjuvant osimertinib now representing the most mature perioperative strategy because it has demonstrated durable disease-free survival, overall survival, and central nervous system (CNS) benefit in ADAURA. This review examines resectable EGFR-mutant NSCLC through the lens of evidence maturity rather than novelty, emphasizing the biologic features that distinguish this subgroup from unselected NSCLC, including CNS tropism, limited perioperative immunotherapy efficacy, and the distinct interpretability of pathologic response under EGFR-tyrosine kinase inhibitor (TKI) therapy. We compare established and emerging perioperative approaches, including aumolertinib, furmonertinib, befotertinib, and neoadjuvant or perioperative osimertinib-based strategies, while underscoring that encouraging early signals should not be equated with established survival benefit before mature event-free survival or overall survival data are available. We also address three unresolved questions: the role of adjuvant chemotherapy in the osimertinib era, the extent to which targeted therapy should move into the neoadjuvant setting, and whether minimal residual disease assessment may eventually support treatment personalization. Overall, current evidence supports adjuvant osimertinib as the reference standard for resected EGFR-mutant NSCLC, whereas other third-generation adjuvant TKIs and perioperative targeted strategies remain promising but should be interpreted according to the maturity of their supporting data and the presence or absence of overall survival benefit.
Revisiting patient preference in resectable and irradiable stage III NSCLC in the immunotherapy era.
Pm P, Ac D, Nm N … +3 more , S P, I O, Dr R
Cancer Treat Rev · 2026 May · PMID 42025542 · Publisher ↗
The optimal local treatment for resectable stage III non-small cell lung cancer (NSCLC) remains controversial, with both surgery and radiotherapy considered valid options depending on tumor characteristics, comorbidities...
The optimal local treatment for resectable stage III non-small cell lung cancer (NSCLC) remains controversial, with both surgery and radiotherapy considered valid options depending on tumor characteristics, comorbidities, and institutional expertise. The introduction of immunotherapy has improved outcomes in surgery- as well as radiotherapy-based treatment approaches. Current ESMO and NCCN guidelines demonstrate both consensus and discrepancies in N2 NSCLC. When both surgery and radiotherapy are feasible, patient preference should be considered in decision-making, supported by multidisciplinary discussion and current evidence.
Interleukin-8: a tumor-agnostic biomarker integrating cancer biology and host response across solid tumors.
Scaglione IM, Bazzichetto C, Borghesani M … +13 more , Zacchi F, Eccher S, Sposito M, Insolda J, Giontella E, Trevisani E, Avancini A, Tregnago D, Cingarlini S, Pilotto S, Conciatori F, Belluomini L, Milella M
Cancer Treat Rev · 2026 May · PMID 41997080 · Publisher ↗
Interleukin-8 (IL-8/CXCL8) drives tumor progression via CXCR1/2 signaling, promoting proliferation, invasion, angiogenesis, and recruitment of pro-tumoral immune and stromal cells. Accumulating clinical evidence indicate...
Interleukin-8 (IL-8/CXCL8) drives tumor progression via CXCR1/2 signaling, promoting proliferation, invasion, angiogenesis, and recruitment of pro-tumoral immune and stromal cells. Accumulating clinical evidence indicates that elevated circulating or intratumoral IL-8 levels are consistently associated with adverse prognosis and reduced therapeutic benefit across principal solid tumors. In particular, IL-8 has emerged as a promising prognostic and predictive biomarker of resistance to immune checkpoint inhibitors. This review highlights its prognostic and predictive value across gastrointestinal, genitourinary, lung, melanoma, breast, ovarian, and head and neck cancers, and discusses strategies targeting IL-8 and the need for standardized, clinically actionable assays.
Multigene assays in early breast cancer: Current evidence, limits and future directions.
Fina E, Lauro VD, Rizzo A … +4 more , Bove S, Comes MC, Laurentiis M, Massafra R
Cancer Treat Rev · 2026 May · PMID 41997079 · Publisher ↗
Recent developments in genomic profiling and molecular diagnostics have significantly improved our comprehension of breast cancer, leading to the advent of personalized treatment options. The evolution of genomic assays,...
Recent developments in genomic profiling and molecular diagnostics have significantly improved our comprehension of breast cancer, leading to the advent of personalized treatment options. The evolution of genomic assays, including Oncotype DX®, MammaPrint®, Prosigna®, EndoPredict®, and Breast Cancer Index®, along with the collaboration of multidisciplinary teams, signifies a transition toward more customized and effective therapeutic strategies. Our work offers a thorough overview of the advancing strategies in breast cancer management in terms of multigene assay application to the clinical routine, specifically focusing on current evidence, limits and future research directions.
Integrin beta-6: Its emerging role as a therapeutic target in solid tumors.
Sanborn RE, Peters S, Barbie D
Cancer Treat Rev · 2026 May · PMID 41990605 · Publisher ↗
Integrins, a family of heterodimeric transmembrane receptors, mediate bidirectional intercellular communication as well as cellular communication with the extracellular matrix. Integrin beta-6 (IB6), which is formed via...
Integrins, a family of heterodimeric transmembrane receptors, mediate bidirectional intercellular communication as well as cellular communication with the extracellular matrix. Integrin beta-6 (IB6), which is formed via exclusive dimerization of the β6 subunit with the αv subunit, is expressed at low levels in healthy epithelial tissues and upregulated during the epithelial remodeling associated with development and wound healing. The role of IB6 in these processes is thought to be exploited during tumorigenesis enabling migration, invasion, proliferation, and survival. In fact, IB6 expression has been reported in numerous solid tumors, particularly at the invasive edge, and IB6 represents a promising anticancer therapeutic target. Over the last two decades, there have been several distinct strategies targeting IB6 investigated in preclinical studies. While many of the early preclinical strategies were discontinued after disappointing results in initial clinical studies, using IB6 as a target for antibody-drug conjugates has shown promise in early trials. Sigvotatug vedotin, an IB6-directed antibody-drug conjugate linked to a monomethyl auristatin E payload showed promising efficacy in a phase 1 study in patients with advanced solid tumors, particularly non-small cell lung cancer, and is being investigated in two phase 3 studies. Additionally, several other IB6-directed antibody-drug conjugates have demonstrated antitumor activity in preclinical studies and are entering the clinical stage of development. Results from these studies will enable greater understanding of IB6 as an anticancer therapeutic target, as well as IB6 expression as a potential biomarker.
Comprehensive genomic profiling in solid tumours: Navigating promise, challenges, and pathways to clinical integration.
Studiale V, Taravella A, Landi M … +4 more , Antoniotti C, Botticelli A, Marchetti P, Cremolini C
Cancer Treat Rev · 2026 May · PMID 41945979 · Publisher ↗
The advent of high-throughput technologies has significantly enhanced our understanding of cancer biology. Genomic profiling methods, now widely and commercially available, have shifted the focus from traditional histolo...
The advent of high-throughput technologies has significantly enhanced our understanding of cancer biology. Genomic profiling methods, now widely and commercially available, have shifted the focus from traditional histology-based classifications and drug development toward the identification of specific molecular alterations, many of which may predict response or resistance to an expanding arsenal of targeted agents and immunotherapies. This paradigm shift has laid the foundation for precision oncology, an approach in which treatments are tailored to actionable molecular targets, sometimes regardless of tumour site of origin, as exemplified by tissue-agnostic strategies. This new framework has subsequently reshaped the design of clinical trials, favouring innovative approaches such as trials that enroll patients with different tumour types sharing common genomic features. These trials often incorporate adaptive cohort designs aligned with the availability of novel drugs, allowing for the early assessment of their antitumour activity across multiple tumour types. As a result, significant regulatory milestones have been achieved, with nine anticancer agents having received tissue-agnostic approvals as of 2025. Despite the achievements of precision oncology, several challenges remain to be addressed. Tumour heterogeneity, the need for robust efficacy endpoints, and the requirement for confirmatory evidence, among other factors, continue to limit the widespread implementation of precision oncology and pose regulatory hurdles. This review discusses key trials supporting the clinical role of comprehensive genomic profiling in solid tumours, examines the evidence behind tissue-agnostic drug approvals, and highlights both the progress achieved and the remaining barriers to fully integrating precision oncology into routine clinical care.
Biomarker-guided immunotherapy in gastric cancer: current insights and future perspectives.
Teixidó Mulet M, Veas Rodriguez J, Terán E … +9 more , Piñol M, Vilardell F, Iglesias M, Hierro C, Calvo M, Matias-Guiu X, Salud A, Tabernero J, Montal R
Cancer Treat Rev · 2026 Apr · PMID 41921305 · Publisher ↗
Gastric and gastroesophageal junction adenocarcinoma (GC) is a biologically challenging malignancy associated with suboptimal clinical outcomes due to limited effective treatment options. The recent incorporation of immu...
Gastric and gastroesophageal junction adenocarcinoma (GC) is a biologically challenging malignancy associated with suboptimal clinical outcomes due to limited effective treatment options. The recent incorporation of immune checkpoint inhibitors (ICIs) into therapeutic algorithms has improved the clinical prospects of subsets of GC patients. However, responses to anti-PD-1/PD-L1 agents remain highly heterogeneous, with only some patients deriving long-term benefits. This variability highlights the importance of identifying optimal biomarkers to enhance patient selection, thereby enabling tailored immunotherapy strategies. Whereas microsatellite instability has demonstrated a potent capacity for predicting immunotherapy benefits in GC, other predictive biomarkers, such as PD-L1 expression, remain suboptimal. Advances in gene expression and epigenetic profiling, liquid biopsy approaches, gut microbiome characterization, and artificial intelligence-driven multimodal algorithms applied to multi-omics or digital pathology are key drivers for the comprehensive characterization of the GC tumour microenvironment (TME), which could be used for better treatment selection. Similarly, elucidating the complex tumour-immune interplay with these technologies will be crucial for the success of novel immunotherapeutic approaches under clinical development, by evaluating alternative immune pathways alone or in combination with current actionable targets of GC. The current review aims to give an overview of the current immunotherapeutic landscape in GC, evaluate standard-of-care and emerging biomarkers of immunotherapy response, and discuss the translational potential of incorporating multi-omic and AI-derived biomarkers into biomarker-enriched clinical decision-making frameworks.
Neoantigen-based dendritic cell vaccines in lung cancer: overcoming immunosuppressive barriers for durable antitumor immunity.
Li Z, Feiyue Z, Luyu H … +3 more , Wenqiang Z, Ismail M, Rueckert JC
Cancer Treat Rev · 2026 Apr · PMID 41921304 · Publisher ↗
Cancer immunotherapies developed based on mechanisms of tumour immune evasion represent a major breakthrough in the history of cancer treatment, capable of reversing T-cell exhaustion induced by tumours through immune ch...
Cancer immunotherapies developed based on mechanisms of tumour immune evasion represent a major breakthrough in the history of cancer treatment, capable of reversing T-cell exhaustion induced by tumours through immune checkpoint blockade. However, the predominant focus on T cells as central players in antitumour immunity may have led to the oversight of the crucial role played by dendritic cells (DCs), which are essential for activating and directing T cells against tumour cells. DCs comprise a diverse group of antigen-presenting cells that play an indispensable role in initiating and regulating both innate and adaptive immune responses. Strategies aimed at modulating DC function to enhance cancer immunotherapy are therefore of critical importance. Beyond the development of novel immune checkpoint inhibitors, neoantigen-based DC vaccines represent a promising approach for developing personalised precision immunotherapies. Here, we review the molecular mechanisms underlying DC immunosuppression within the lung tumour microenvironment, how tumour-infiltrating DCs influence immunity and tolerance in the cancer setting, the mechanisms by which tumour-specific neoantigens elicit immune responses, the identification of neoantigens, and recent clinical advances in neoantigen-targeted vaccines for lung cancer. We also discuss recent progress in DC vaccine-based cancer immunotherapies from both preclinical studies and clinical trials.
Hematological immune-related adverse events associated with checkpoint inhibitors.
Janson M, Cherifi F, Bardet H … +1 more , Damaj G
Cancer Treat Rev · 2026 Apr · PMID 41905276 · Publisher ↗
BACKGROUND: The use of immune checkpoint inhibitors (ICIs) has expanded substantially across tumor types, establishing them as a cornerstone of modern oncology. However, the frequency and severity of immune-related adver...
BACKGROUND: The use of immune checkpoint inhibitors (ICIs) has expanded substantially across tumor types, establishing them as a cornerstone of modern oncology. However, the frequency and severity of immune-related adverse events (irAEs) remain underestimated, particularly hematologic toxicities, which can be life-threatening and require distinct management approaches compared to cytotoxic or targeted therapies. METHODS: We performed literature reviews using PubMed to identify and analyze reported cases of the most frequent hematologic irAEs; autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and pure red cell aplasia (PRCA), in patients with solid tumors. In parallel, we report three illustrative cases from our institution to highlight diagnostic pitfalls and management strategies. RESULTS: The median onset of hematologic irAEs occurs after approximately 3 cycles of ICI therapy for AIHA and ITP, and after 4 cycles for PRCA. Most patients achieved remission with corticosteroid therapy; however, 10-15% were steroid-refractory or relapsed, requiring second-line immunosuppressive agents. Rechallenge with ICIs remains controversial due to a recurrence rate of irAE, although it may be feasible and clinically beneficial in carefully selected patients. CONCLUSION: As the use of ICIs continues to rise, prompt recognition and management of hematologic irAEs are critical to minimize morbidity and to avoid premature discontinuation of immunotherapy. Increased clinician awareness and standardized diagnostic algorithms are essential to preserve both safety and efficacy.
Physical activity reduces all-cause mortality in patients with cancer: a systematic review and meta-analysis of randomized controlled trials.
Guillermou H, Diallo A, Rathat G … +1 more , Galtier F
Cancer Treat Rev · 2026 Apr · PMID 41894932 · Publisher ↗
INTRODUCTION: Growing evidence suggests that physical activity (PA) may improve survival in patients with cancer. However, causal evidence from randomized controlled trials (RCTs) remains limited. This systematic review...
INTRODUCTION: Growing evidence suggests that physical activity (PA) may improve survival in patients with cancer. However, causal evidence from randomized controlled trials (RCTs) remains limited. This systematic review and meta-analysis aims to evaluate the effect of PA on all-cause mortality in patients with cancer based on RCTs evidence. METHODS: MEDLINE and CENTRAL were searched without language restrictions up to November 30, 2025. Eligibility criteria included RCTs of PA interventions reporting mortality outcomes in adult cancer patients. The risk of bias in included studies was assessed using the Cochrane Risk of Bias tool for randomized trials (RoB 2), and the quality of the studies was checked with GRADE, by two independent reviewers. Pooled hazard ratios (HRs) were calculated using inverse-variance common-effects models. The study protocol is available at PROSPERO (registration number CRD42023486651). RESULTS: Thirteen RCTs involving 3282 patients with cancer were included. PA reduced all-cause mortality risk by 26% compared to no PA (pooled HR 0.74, 95% CI 0.63 to 0.87, p < 0.001, with moderate quality of evidence), with non-significant heterogeneity (p = 0.21). Subgroup analyses showed consistent effects regardless of intervention duration (≥6 weeks: HR = 0.74; 95% CI: 0.63-0.87; <6 weeks: HR = 0.73; 95% CI: 0.43-1.22; p = 0.93) or hormone dependent status of cancer (non-hormonally dependent: HR = 0.75; 95% CI: 0.63-0.91; hormonally dependent: HR = 0.71; 95% CI: 0.50-1; p = 0.75). Overall, the risk of bias was moderate. CONCLUSIONS: This meta-analysis of RCTs provides causal evidence that PA improves survival in cancer patients, reducing all-cause mortality by 26% (moderate quality of evidence). The results suggest that, in addition to its well-established supportive care benefits, PA should also be recommended as a part of comprehensive disease management in oncology.
Targeted therapeutic strategies in rare subtypes of pancreatic cancer: Histology, molecular profiles, and emerging opportunities.
Scarlato E, Dusetti N, Melisi D
Cancer Treat Rev · 2026 Apr · PMID 41886796 · Publisher ↗
Pancreatic cancer remains one of the deadliest malignancies, with a 5-year survival below 13% and limited response to standard therapies. Conventional pancreatic ductal adenocarcinoma (PDAC), which accounts for over 90%...
Pancreatic cancer remains one of the deadliest malignancies, with a 5-year survival below 13% and limited response to standard therapies. Conventional pancreatic ductal adenocarcinoma (PDAC), which accounts for over 90% of cases, dominates the landscape. Yet rare subsets of histological and molecular variants - such as medullary, colloid, intraductal papillary mucinous neoplasm-associated, and acinar cell carcinomas - have distinct biology and actionable alterations. These tumors are more frequently KRAS wild-type and are enriched for homologous recombination deficiency, DNA mismatch repair defects, microsatellite instability-high status, and, notably, recurrent gene fusions, unveiling promising opportunities for precision-guided therapies in a disease that has long been resistant to standard approaches. These molecular features identify subgroups more likely to benefit from platinum-based chemotherapy, PARP inhibition, immune checkpoint blockade, or targeted agent approaches with limited activity in unselected, conventional PDAC. Emerging stratifications, including MAPK pathway status and age at diagnosis, further refine the identification of actionable subgroups. Although limited, clinical evidence, including basket trials and real-world observations, demonstrates that biomarker-guided interventions can yield meaningful and durable responses, with improved progression-free and overall survival. Incorporating a structured diagnostic algorithm that recognizes rare subtypes and integrating comprehensive genomic profiling into routine practice represents a paradigm shift from non-stratified to mechanism-driven therapy in pancreatic cancer. This narrative review summarizes the clinicopathological characteristics, molecular landscapes, and therapeutic opportunities of rare PDAC subtypes, highlighting how precision medicine can reshape prognosis and treatment in a historically hard-to-treat disease.
The interplay of clonal hematopoiesis and cancer: Clinical implications in oncology.
Tanguay M, Tagliamento M, Samaniego J … +4 more , Besse B, Renneville A, Bernard E, Micol JB
Cancer Treat Rev · 2026 Apr · PMID 41791906 · Publisher ↗
Clonal hematopoiesis (CH) refers to the expansion of hematopoietic stem and progenitor cells carrying somatic mutations and is increasingly identified in oncology through cell-free DNA testing. Once regarded mostly as a...
Clonal hematopoiesis (CH) refers to the expansion of hematopoietic stem and progenitor cells carrying somatic mutations and is increasingly identified in oncology through cell-free DNA testing. Once regarded mostly as a precursor to myeloid neoplasms and a contributor to cardiovascular disease, CH is now recognized as a major determinant of clinical outcomes in patients with cancer. Specific anticancer agents selectively promote the expansion of clones with DNA damage response gene mutations, particularly those with TP53 or PPM1D mutations, which are strongly associated with myeloid neoplasms post cytotoxic therapy (MN-pCT). The extent of clonal growth varies with treatment and, in some cases, may regress once therapy is withdrawn. In addition to therapy-driven clonal selection, inflammatory stress accelerates clonal expansion, creating a self-reinforcing cycle that contributes to atherosclerosis and other inflammation-associated complications. In oncology, CH-derived immune cells can infiltrate the tumor microenvironment and remodel local immunity, influencing tumor growth and treatment response. This tissue-infiltrating form of CH, termed tumor-infiltrating CH, has been associated with inferior survival in some cancer cohorts. Together, these findings establish CH as both a clinical challenge and an opportunity in modern oncology. Dedicated CH clinics and molecular tumor boards are emerging to address its implications for risk stratification, treatment selection, and survivorship care. This review examines the biology and clinical impact of CH in oncology, including its mutational spectrum, clonal evolution, role in MN-pCT, effects on inflammation and the tumor microenvironment, and emerging strategies for risk assessment and patient management.
Erratum to "Impact of brain metastases on systemic renal cell carcinoma treatment outcomes: A systematic literature review". [Cancer Treat. Rev. 140 (2025) 103024].
Charnley N, Fife K, Heng DYC … +9 more , Larkin J, McGrane J, Négrier S, Vasudev N, Venugopal B, Chisholm A, Ogareva A, Prendergast Á, Albiges L
Cancer Treat Rev · 2026 Mar · PMID 41781237 · Publisher ↗
Abstract loading — click title to view on PubMed.
Diagnosis and treatment of human epidermal growth factor receptor 2-positive metastatic colorectal cancer: a systematic literature review.
Siena S, Chalabi M, Goodwin R … +6 more , Osterlund P, Penault-Llorca F, Sartore-Bianchi A, Starling N, Stintzing S, Tabernero J
Cancer Treat Rev · 2026 Mar · PMID 41763144 · Publisher ↗
Human epidermal growth factor receptor 2 (HER2)-targeted therapies have been investigated for therapeutic benefit in RAS/BRAF wild-type/HER2+ metastatic colorectal cancer (mCRC). Unlike HER2+ breast and gastric cancer, t...
Human epidermal growth factor receptor 2 (HER2)-targeted therapies have been investigated for therapeutic benefit in RAS/BRAF wild-type/HER2+ metastatic colorectal cancer (mCRC). Unlike HER2+ breast and gastric cancer, there are no regulatory criteria for determining HER2 overexpression in patients with mCRC. This systematic literature review describes unmet needs for patients with HER2+ mCRC in relation to testing and treatment, highlights the importance of early HER2 testing at mCRC diagnosis, and discusses the evolving treatment landscape. We utilised PubMed and EMBASE databases up to November 2023 to identify journal articles and published congress abstracts relating to the HER2+ disease and treatment landscape, HER2 testing in mCRC, and HER2-targeted treatments in mCRC. Many studies have demonstrated the utility of immunohistochemistry, in situ hybridisation, and next-generation sequencing (tissue- and circulating tumour DNA-based) for detecting HER2 overexpression/amplification in mCRC and have attempted to establish consolidated criteria like those used for breast and gastric cancer. The value of HER2-targeted treatments in patients with HER2+ mCRC has been evidenced by clinical trials and meta-analyses, with strong evidence from MOUNTAINEER and DESTINY-CRC01 which supports the use of tucatinib + trastuzumab or trastuzumab deruxtecan, respectively, among this patient population. However, real-world analyses have confirmed that patients with HER2+ mCRC are not routinely tested for HER2 overexpression. Strong evidence and clinical guidelines support the value of HER2-targeted treatment among patients with HER2+ mCRC. There is a need for increased awareness and earlier uptake of HER2 testing among patients with mCRC to broaden treatment options and optimise outcomes for this patient population.
Immunotherapy with anti-PD-1 or PD-L1 in advanced ovarian cancer: A meta-analysis of randomized trials.
Vida R, Bartoletti M, Montico M … +8 more , Pignata S, Baldassarre G, Ditto A, Zapelloni G, Rizzetto M, Lay L, Margherita P, Puglisi F
Cancer Treat Rev · 2026 Mar · PMID 41763143 · Publisher ↗
BACKGROUND: Ovarian cancer remains the gynecological malignancy with the highest mortality rate. Despite advances in treatment, the median overall survival remains suboptimal. Although there is strong biological rational...
BACKGROUND: Ovarian cancer remains the gynecological malignancy with the highest mortality rate. Despite advances in treatment, the median overall survival remains suboptimal. Although there is strong biological rationale for the use of immune checkpoint inhibitors (ICIs), their clinical efficacy in ovarian cancer remains uncertain. This study aimed to evaluate the effectiveness of anti-PD-1/PD-L1 agents in advanced ovarian cancer by reviewing randomized trials. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Data sources included PubMed, EMBASE, the Cochrane Library, and major conference abstracts, with searches conducted up to July 1, 2025. Eligible studies included RCTs comparing anti-PD-1/PD-L1 agents (with or without chemotherapy) to standard treatments in patients with advanced ovarian cancer (first-line, platinum-sensitive, or platinum-resistant). Trials with fewer than 50 patients or non-randomized designs were excluded. Two authors independently extracted summary-level data. The primary outcome measure was progression-free survival (PFS) in the intention-to-treat population. A random-effects model was used to estimate pooled hazard ratios (HRs). Risk of bias was assessed using the Cochrane RoB 2 tool. (Supplementary, Fig. S1) The meta-analysis was registered with PROSPERO (CRD420251112816). FINDINGS: Ten RCTs (n = 7,847 patients) met the inclusion criteria. Overall, ICIs did not significantly improve PFS compared to control treatments (HR 0.98, 95% CI 0.85-1.12; I = 67%). No significant benefit was observed in either first-line (HR 0.93) or recurrent settings (HR 1.07), nor in PD-L1-positive, BRCA-mutated, or homologous recombination deficiency (HRD) populations. A non-significant trend favouring ICI + PARP inhibitor combinations was observed in HR-proficient patients (HR 0.77, 95% CI 0.65-0.92). Sensitivity analyses confirmed the robustness of the findings. Overall survival (OS) data were either immature or not reported in most trials. The risk of bias was rated as low to moderate across studies, although there was high heterogeneity. INTERPRETATION: Anti-PD-1/PD-L1-based ICI strategies have not led to significant improvements in outcomes for ovarian cancer. Future studies should focus on optimizing biomarker selection, evaluating combination therapies, and targeting the tumor microenvironment to enhance the efficacy of immunotherapy. FUNDING: This research received no external funding.
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