Cancer Treat. Rev. [JOURNAL]
Sun
200 papers
First versus second-generation molecular profiling tests: How both can guide decision-making in early-stage hormone-receptor positive breast cancers?
Nguyen Van Long F, Poirier B, Desbiens C … +6 more , Perron M, Paquet C, Ouellet C, Diorio C, Lemieux J, Nabi H
Cancer Treat Rev · 2025 Apr · PMID 40054315 · Publisher ↗
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) tumors represent the most common types of early-stage breast cancer. However, their response to adjuvant systemic treatments v...
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) tumors represent the most common types of early-stage breast cancer. However, their response to adjuvant systemic treatments varies widely due to tumor heterogeneity. Current decisions for adjuvant treatment rely heavily on clinical and pathological characteristics, which can sometimes lead to overtreatment. Accurately identifying patients who will benefit from adjuvant chemotherapy at an individual level remains a challenge. Multigene profiling assays are now widely used in clinics to better assess recurrence risk and chemotherapy response for HR+ disease. In this report, we examine the advantages and limitations of two widely used molecular profiling tests-Oncotype DX and Prosigna. Both Oncotype DX and Prosigna have been demonstrated to be effective prognostic tools in early breast cancer, with Oncotype DX also being validated as a predictive tool to guide chemotherapy decisions. We focus on studies that directly compare these molecular tests and discuss how their strengths can be leveraged to improve clinical decision-making for early-stage HR+ breast cancers. Finally, we highlight remaining knowledge gaps and propose directions for future research.
Assessment and stratification of cardiovascular disease risk in people diagnosed with breast cancer: A scoping review.
Jeon MH, DiSipio T, Wilson L … +2 more , Garvey G, Diaz A
Cancer Treat Rev · 2025 Apr · PMID 40054314 · Publisher ↗
BACKGROUND: Breast cancer patients are at increased risk of cardiovascular disease, which often are associated with cardiotoxic breast cancer treatment or overlapping risk factors between the two diseases. Pre-treatment...
BACKGROUND: Breast cancer patients are at increased risk of cardiovascular disease, which often are associated with cardiotoxic breast cancer treatment or overlapping risk factors between the two diseases. Pre-treatment cardiovascular risk assessment can enable accurate risk stratification and prevention of cardiovascular disease. Several tools have been suggested, described or used in research to assess baseline (pre-treatment) risk to determine appropriate cardiovascular disease care before, during and after cancer treatment. This scoping review aims to identify and describe key features of baseline cardiovascular disease risk assessment tools for breast cancer patients. METHODS: PubMed, Embase and Google Scholar were searched for articles published January 2013 - March 2024 to identify publications reporting cardiovascular disease risk assessment tools in breast cancer patients. Publications included research articles (observational and experimental studies) and position/policy, commentary and review papers. Eligibility was assessed and key data were extracted independently by two reviewers. Conflicts were discussed and resolved with the authorship team. RESULTS: A total 144 articles were identified. Of these, 57 reported original data for the development, validation or recommendations of cardiovascular disease risk assessment tools and 87 reported the use of such tools. From these articles, 13 tools were identified that assessed the risk of cardiovascular disease broadly (n = 3) or death due to cardiovascular disease (n = 1) or specifically of cardiotoxicity or heart failure (n = 8) or venous thromboembolism (n = 1) in people diagnosed with breast cancer. Fourteen tools assessed cardiovascular disease risk in people diagnosed with mixed cancer types, including breast cancer. The planned development of four tools and/or surveillance pathways were described in protocol papers. Among all these tools identified (n = 31), seven tools (among these, four tools assessed people diagnosed with breast cancer only) went through external validation and performed poorly or moderately in stratifying cancer patients effectively into risk categories. Risk factors included in the assessment tools were age, breast cancer treatment type and pre-existing cardiovascular disease. While clinical guidelines and recommendations about baseline cardiovascular disease risk assessment were identified, these were either for cancer patients broadly or for cancer treatment types, and not specifically for people diagnosed with breast cancer. CONCLUSION: Several tools to assess baseline cardiovascular disease in people diagnosed with breast cancer were identified but only seven tools had gone through a validation process, and none were found to be very effective in differentiating people by baseline cardiovascular disease risk. Further work is needed to optimise the effectiveness of baseline cardiovascular disease risk assessments for breast cancer patients to enable appropriate stratification and monitoring of risk before, during and after treatment to improve cardiovascular health and outcomes.
Current controversies in the use of Oncotype DX in early breast cancer.
Berton Giachetti PPM, Carnevale Schianca A, Trapani D … +9 more , Marra A, Toss A, Marchiò C, Dieci MV, Gentilini OD, Criscitiello C, Kalinsky K, Sparano JA, Curigliano G
Cancer Treat Rev · 2025 Apr · PMID 40048856 · Publisher ↗
Multigene prognostic genomic assays have become essential tools in the management of early breast cancer (BC), providing information that help in risk-stratification, to provide risk-adapted decision-making of adjuvant t...
Multigene prognostic genomic assays have become essential tools in the management of early breast cancer (BC), providing information that help in risk-stratification, to provide risk-adapted decision-making of adjuvant treatments. Clinical practice guidelines recommend refining the prognostic information provided by clinical and pathology features with the use of genomic tests, such as Oncotype DX®, to classify cancers into risk groups and inform adjuvant treatment strategies. However, the clinical value (i.e., prognostic and/or predictive) and applicability of these assays vary due to differences in the clinical setting, especially in those populations that were underrepresented in pivotal clinical trials. Oncotype DX® is a broadly utilized genomic test for breast cancer, having the highest level of supporting evidence to inform clinical practice. Our manuscript provides a comprehensive overview on this recurrence score assay, evaluates supporting evidence across patient populations, and discusses their impact on treatment decisions in those groups of patients underrepresented in pivotal clinical trials, where evidence is limited with the use of Oncotype DX.
Functioning neuroendocrine tumors (NET): Minimum requirements for a NET specialist.
Spada F, Rossi RE, Modica R … +6 more , Gelsomino F, Rinzivillo M, Rubino M, Pisa E, La Salvia A, Fazio N
Cancer Treat Rev · 2025 Apr · PMID 40023966 · Publisher ↗
INTRODUCTION AND AIMS: Functioning neuroendocrine tumors (f-NETs) represent a minority of all NETs, however their management is challenging due to the impact on patients' survival and quality of life. In addition to f-NE...
INTRODUCTION AND AIMS: Functioning neuroendocrine tumors (f-NETs) represent a minority of all NETs, however their management is challenging due to the impact on patients' survival and quality of life. In addition to f-NETs, paraneoplastic syndromes (PNS) are due to substances that are not related to the primary anatomical site, they can develop in different phases of NETs evolution, and might complicate the patient's clinical course. Dedicated guidelines are still scanty. We aim to review available literature on f-NETs to propose a useful tool for clinicians in order to improve the diagnostic process and the management. METHODS: Narrative review focused on f-NETs. RESULTS: The most common f-NETs include insulinomas, gastrinomas and carcinoid syndrome (CS)- associated NETs. Symptoms related to hormone production may overlap with other common endocrine and gastrointestinal disorders, highlighting the pivotal role of multidisciplinary management. Somatostatin analogs (SSAs) represent the gold standard first-line treatment of most f-NETs, often followed by or combined with other treatments (surgery, liver-directed therapies, targeted therapies, peptide receptor radionuclide therapy). Paraneoplastic syndromes can develop in different phases of NET evolution and might complicate the patient's clinical course and response to therapy. CONCLUSIONS: The management of hormonal syndromes is challenging and must be based on the multidisciplinary approach. Herein, we pointed out the minimal requirements for a NET specialist in the diagnosis and treatment of f-NETs. Efforts should be made to improve the awareness of functioning forms, to understand their pathogenesis and to improve their management.
Therapeutic advances in Tenosynovial giant cell Tumor: Targeting the CSF1/CSF1R axis.
Assi T, Moussa T, Ngo C … +9 more , Faron M, Verret B, Lévy A, Honoré C, Hénon C, Péchoux CL, Bahleda R, Vibert J, Cesne AL
Cancer Treat Rev · 2025 Mar · PMID 40020639 · Publisher ↗
Tenosynovial giant cell tumor is a non-malignant primary locally aggressive articular disease that affects the synovium of joints, tendon sheaths, and bursae. It is characterized by a translocation t (1;2), leading to th...
Tenosynovial giant cell tumor is a non-malignant primary locally aggressive articular disease that affects the synovium of joints, tendon sheaths, and bursae. It is characterized by a translocation t (1;2), leading to the overexpression of CSF1 in the tumor microenvironment. CSF1 induces the recruitment of non-malignant cells, mainly macrophages, followed by the differentiation and polarization of these cells into the M2 phenotype. Surgery, particularly total synovectomy, remains the cornerstone of TGCT management. However, recurrence rates vary, reaching 40 to 60% in diffuse disease, often resulting in progressive joint dysfunction, pain, and potential need for joint replacement or limb amputation. Systemic therapy is recommended in recurrent TGCT in patients not amenable to additional surgery. Targeting the CSF1/CSF1R axis has successfully improved tumor responses and enhanced symptomatic function. In this review, we aim to explore contemporary paradigms in inoperable TGCT patients, with a focus on the physiopathology, clinical efficacy, and safety of CSF1 or CSF1R inhibitors.
BRAFV600E mutant metastatic colorectal cancer: Current advances in personalized treatment and future perspectives.
Napolitano S, Ciardiello D, Cioli E … +7 more , Martinelli E, Troiani T, Giulia Zampino M, Fazio N, De Vita F, Ciardiello F, Martini G
Cancer Treat Rev · 2025 Mar · PMID 40009904 · Publisher ↗
Detection of the BRAF V600E mutation has important genetic, prognostic, and therapeutic implications for patients with metastatic colorectal cancer (mCRC), identifying a subgroup of patients who derive modest benefit fro...
Detection of the BRAF V600E mutation has important genetic, prognostic, and therapeutic implications for patients with metastatic colorectal cancer (mCRC), identifying a subgroup of patients who derive modest benefit from standard treatments and have extremely poor prognosis. The evolution of molecular profiling and the implementation of next generation sequencing in the evaluation of a patient with BRAF-mutated mCRC has currently led to the discovery of actionable alterations. Targeting multiple pathways of resistance in BRAF-mutated mCRC may be the most efficacious route. Then, over a short period of time, the treatment landscape BRAF-mutated mCRC patients has shifted dramatically. Finally, novel treatment strategies are available. This review will discuss on currently approved treatments for BRAF V600E mutated mCRC and will try and portray the changing landscape in this setting in the era of targeted molecular therapy.
Individualizing first-line treatment for advanced urothelial carcinoma: A favorable dilemma for patients and physicians.
Grande E, Hussain SA, Barthélémy P … +5 more , Kanesvaran R, Giannatempo P, Benjamin DJ, Hoffman J, Birtle A
Cancer Treat Rev · 2025 Mar · PMID 39999590 · Publisher ↗
The treatment landscape for patients with advanced urothelial carcinoma (UC) has evolved rapidly in recent years. In current guidelines, combination treatment with enfortumab vedotin plus pembrolizumab is the first-line...
The treatment landscape for patients with advanced urothelial carcinoma (UC) has evolved rapidly in recent years. In current guidelines, combination treatment with enfortumab vedotin plus pembrolizumab is the first-line (1L) standard of care, and other recommended 1L treatment options are platinum-based chemotherapy followed by avelumab as switch-maintenance treatment in patients without progression, or combination treatment with nivolumab, cisplatin, and gemcitabine for cisplatin-eligible patients only. Individual patients differ in terms of their health status, disease characteristics, expected toxicities, and treatment preferences; thus, a "one-size-fits-all" approach to treatment is unlikely to be optimal. The availability of several treatment options creates the potential for individualized treatment. In this review, we discuss factors that may be considered when selecting 1L treatment for patients with advanced UC, including efficacy and safety data from phase 3 trials and real-world studies, quality of life, patient priorities for treatment, patient and disease characteristics, treatment sequencing, biomarkers, and treatment access and cost. Patients and physicians should discuss the benefit-risk balance of all available 1L options to enable shared decision-making. Longer follow-up from clinical trials and additional real-world studies are needed to further inform treatment selection.
Comparative efficacy and safety of pyrotinib plus trastuzumab versus trastuzumab plus pertuzumab and trastuzumab monotherapy in neoadjuvant treatment of HER2-positive breast cancer: A systematic review and meta-analysis.
Yuan Y, Liu X, Xu G … +3 more , Zhang J, Chen L, Long X
Cancer Treat Rev · 2025 Mar · PMID 39986012 · Publisher ↗
INTRODUCTION: HER2-positive breast cancer is an aggressive subtype that benefits from targeted therapies. Some studies have shown that pyrotinib (P) plus trastuzumab (H) has a good efficacy against early or locally advan...
INTRODUCTION: HER2-positive breast cancer is an aggressive subtype that benefits from targeted therapies. Some studies have shown that pyrotinib (P) plus trastuzumab (H) has a good efficacy against early or locally advanced HER2-positive breast cancer. However, there is still no systematic review and meta-analysis supporting the efficacy and safety of pyrotinib plus trastuzumab versus standard regimens in the neoadjuvant treatment of early or locally advanced breast cancer. This study is the first systematic review and meta-analysis to compare the efficacy and safety of pyrotinib combined with trastuzumab versus trastuzumab combined with pertuzumab (Per) and trastuzumab monotherapy in the neoadjuvant treatment of HER2-positive breast cancer. METHODS: We conducted a systematic literature search in PubMed, Embase, the Cochrane Library, CNKI, Wan Fang and VIP databases for relevant studies published up to August 30th, 2024. RCTs, cohort studies and retrospective studies with HER2-positive breast cancer patients who had not received breast cancer-related treatments previously were included. Treatment of P + H, H or Per + H arms with chemotherapy combined with pyrotinib plus trastuzumab, trastuzumab or pertuzumab plus trastuzumab as neoadjuvant treatment. The primary outcome was the total pathological complete response (tpCR), and secondary outcomes included breast pathological complete response (bpCR), ORR, DCR, and grade III/IV AEs. The quality of evidence was assessed using the GRADE. RESULTS: A total of nine studies (4 RCTs, 1 prospective cohort study and 4 retrospective analysis) involving 1745 patients were included. The P + H arm showed no significant difference in tpCR compared to Per + H (RR: 0.94, 95 % CI: 0.80-1.11, p = 0.46) but demonstrated a significant improvement in tpCR over trastuzumab monotherapy (RR: 1.83, 95 % CI: 1.56-2.15, p < 0.001). This finding was further confirmed in meta-analysis of RCTs (RR: 1.87, 95 % CI: 1.42-2.47, p < 0.001). The P + H arm had a higher incidence of grade III/IV diarrhea (RR: 10.54, 95 % CI: 5.96-18.63, p < 0.001) but similar rates of other AEs compared to the H arm. The evidence quality for tpCR (P + H vs. H, RCT) was high, and that for tpCR (P + H vs. H) was moderate, while that for tpCR (P + H vs. Per + H) was low. CONCLUSIONS: Pyrotinib combined with trastuzumab may offer an effective neoadjuvant treatment option for HER2-positive breast cancer, with a superior efficacy over trastuzumab alone. However, pyrotinib plus trastuzumab did not show better efficacy compared with Per + H. Pyrotinib plus trastuzumab was associated with more diarrhrea than trastuzumab monotherapy. In addition, P + H is less cost-effective compared with the combination of Per + H.
Antibody-drug conjugates in NSCLC with actionable genomic alterations: Optimizing smart delivery of chemotherapy to the target.
Mountzios G, Saw SPL, Hendriks L … +10 more , Menis J, Cascone T, Arrieta O, Naidoo J, Koutoukoglou P, Cani M, Lefevre A, Addeo A, Peters S, Remon J
Cancer Treat Rev · 2025 Mar · PMID 39978083 · Publisher ↗
The advent of antibody-drug conjugates (ADCs) aims to transform the therapeutic landscape of advanced non-small cell lung cancer (NSCLC). The distinctive architecture of ADCs enables the targeted delivery of highly poten...
The advent of antibody-drug conjugates (ADCs) aims to transform the therapeutic landscape of advanced non-small cell lung cancer (NSCLC). The distinctive architecture of ADCs enables the targeted delivery of highly potent cytotoxic payloads directly to cancer cells that express the molecular target specified by their monoclonal antibody component. This precision targeting stems from the notion that ADCs may be highly effective therapeutic agents, particularly for treating NSCLC tumors harboring actionable genomic alterations (AGAs). In this context, ADCs can be categorized into two main types: Biomarker-selected ADCs, which require the tumor to present a specific pattern of the protein targeted by the ADC (e.g., MET overexpression, HER2 overexpression or mutation) and formally requiring biomarker testing, and biomarker-agnostic ADCs, which target proteins that are broadly expressed in lung cancer cells (e.g., anti-TROP2 or HER.3 ADCs), and hence no pre-testing is required. The cytotoxic payload is expected to be delivered in high concentration in the cancer cells carrying the corresponding target of interest, while minimizing off-target toxicity. In this review, we describe available evidence regarding the efficacy and safety of ADCs in NSCLC harboring AGAs. We also discuss the challenges with respect to appropriate biomarker selection, dose optimization, treatment duration, and optimization of the structural design of ADC components to maximize efficacy while minimizing off-target toxicity. Finally, addressing cost-effectiveness concerns remains critical for their successful adoption within healthcare systems.
Practical clinical management of ocular adverse events related to Antibody-Drug Conjugates in gynaecological malignancies.
Bouguerra Zina B, Rousseau F, Fauquier S … +2 more , Sabatier R, Kfoury M
Cancer Treat Rev · 2025 Mar · PMID 39970828 · Publisher ↗
BACKGROUND: The advent of Antibody-Drug Conjugates (ADC) represents a significant advancement in targeted therapy for gynaecological malignancies. However, the ocular toxicities associated with ADCs, particularly Tisotum...
BACKGROUND: The advent of Antibody-Drug Conjugates (ADC) represents a significant advancement in targeted therapy for gynaecological malignancies. However, the ocular toxicities associated with ADCs, particularly Tisotumab Vedotin (TV) and Mirvetuximab Soravtansine (MIRV) necessitate effective mitigation in order to optimise patient care. METHODS: This review synthesises findings from clinical trials to delineate the spectrum of ocular adverse events induced by ADCs. The analysis focuses on the incidence, onset, severity and reversibility of adverse events. It examines the underlying mechanisms of toxicity and provides management strategies based on study protocols. RESULTS: Adverse events mainly impact the anterior ocular segment, resulting in conjunctivitis and keratopathy. They affect up to 56 % of patients treated with MIRV and 50 to 60 % of those receiving TV. Symptoms like blurred vision, dryness and pain hinder the patient's quality of life. Events are CTCAE grade 3 or higher in less than 10 % of cases. The median time to onset is 1.3 months. However, ocular toxicity may appear up to 10 months after treatment initiation, indicating a need for prolonged vigilance. Primary prophylaxis calls for local corticotherapy, lubricants and in some cases, vasoconstrictors. Despite the potential for severity, most cases are reversible with local treatment and transient dose reduction and/or delay. Close monitoring is crucial for early detection and subsequent management. CONCLUSIONS: Clinicians ought to be cognizant of the potential ocular toxicity of ADCs. Proactive prophylaxis, patient education and a multidisciplinary approach involving ophthalmologists are paramount to minimising the impact of these AEs. Further research is essential to measure the real outcome of preventive strategies and balance their benefits with potential short and long-term risks.
Melanoma-associated antigen A4: A cancer/testis antigen as a target for adoptive T-cell receptor T-cell therapy.
Knafler G, Ho AL, Moore KN … +3 more , Pollack SM, Navenot JM, Sanderson JP
Cancer Treat Rev · 2025 Mar · PMID 39970827 · Full text
T-cell receptor (TCR) T-cell therapies are adoptive cell therapies in which patient cells are engineered to express TCRs targeting specific cancer antigens and infused back into the patient. Since TCR recognition depends...
T-cell receptor (TCR) T-cell therapies are adoptive cell therapies in which patient cells are engineered to express TCRs targeting specific cancer antigens and infused back into the patient. Since TCR recognition depends on antigen presentation by the human leukocyte antigen system, TCRs can respond to intracellular antigens. Cancer/testis antigens (CTAs) are a large family of proteins, many of which are only expressed in cancerous tissue and immune-privileged germline sites. Melanoma-associated antigen A4 (MAGE-A4) is an intracellular CTA expressed in healthy testis and placenta, and in a range of cancers, including esophageal, head and neck, gastric, ovarian, colorectal, lung, endometrial, cervical, bladder, breast and prostate cancers; soft tissue sarcomas; urothelial and hepatocellular carcinomas; osteosarcoma; and melanoma. This expression pattern, along with the immunogenicity and potential role in tumorigenesis of MAGE-A4 make it a prime target for TCR T-cell therapy. We outline the preclinical and clinical development of TCR T-cell therapies targeting CTAs for treatment of solid tumors, highlighting the need for extensive preclinical characterization of putative off-target, and potential on-target but off-tumor, effects. We identified ten clinical trials assessing TCR T-cell therapies targeting MAGE-A4. Overall, manageable safety profiles and signals of efficacy have been observed, especially in patients with advanced synovial sarcoma, myxoid/round cell liposarcoma, ovarian, head and neck, and urothelial cancers, with one TCR T-cell therapy approved by the US Food and Drug Administration in August 2024. We also review the limitations, and strategies to enhance efficacy and improve safety, of these therapies, and summarize related immunotherapies targeting MAGE-A4.
The efficacy of streptozotocin in managing pancreatic neuroendocrine neoplasms - A systematic review.
Arrivi G, Fazio N, Tafuto S … +5 more , Falconi M, Carnaghi C, Campana D, Rinzivillo M, Panzuto F
Cancer Treat Rev · 2025 Mar · PMID 39954330 · Publisher ↗
Pancreatic neuroendocrine tumors (pan-NETs) represent a highly heterogeneous and complex pathology, with therapeutic management and prognosis influenced by several biological and clinical characteristics. Chemotherapy, i...
Pancreatic neuroendocrine tumors (pan-NETs) represent a highly heterogeneous and complex pathology, with therapeutic management and prognosis influenced by several biological and clinical characteristics. Chemotherapy, including regimens based on capecitabine and temozolomide (CAPTEM) or the combination of streptozotocin and 5-fluorouracil (STZ-5FU), is indicated for rapidly growing, symptomatic, or high-burden disease requiring swift cytoreduction. Historical studies provide scientific evidence for the STZ-5FU regimen, often retrospective and frequently analyzing small series. Despite these limitations, the efficacy of this treatment is well-established, and it is included in all guidelines as a therapeutic option. This systematic review aims to gather scientific evidence on using STZ-based chemotherapy to assess its real impact in managing well-differentiated metastatic or unresectable pan-NETs.
Primary mediastinal large B-cell Lymphoma: Biological features, clinical characteristics and current treatment strategies.
Donzelli L, Rocco AD, Petrucci L … +1 more , Martelli M
Cancer Treat Rev · 2025 Mar · PMID 39947011 · Publisher ↗
Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct subtype of B-cell lymphoma, representing a clinical and therapeutic challenge due to its unique presentation, histopathological features, and treatment resp...
Primary mediastinal large B-cell lymphoma (PMBCL) is a distinct subtype of B-cell lymphoma, representing a clinical and therapeutic challenge due to its unique presentation, histopathological features, and treatment response. It primarily affects young adults, with a significant female preponderance, and is characterized by a large anterior mediastinal mass that causes compressive symptoms. Despite its aggressive nature, PMBCL patients have a favorable prognosis, with a 5-year survival rate exceeding 80% when early remission is achieved through first-line therapy. Drawing on the significant scientific therapeutic advances over recent years, this review focuses on the evolving treatment strategies for PMBCL patients. Anthracycline- and rituximab-containing regimens are the mainstays of first-line approaches, often followed by mediastinal radiation therapy. However, concerns regarding long-term toxicities have led to a reevaluation of treatment protocols, suggesting that radiotherapy can be safely omitted in patients who achieve a complete metabolic response after induction therapy, according to a PET-guided approach. Furthermore, new targeted therapies such as PD-1 inhibitors and CAR-T cell immunotherapy, have shown promising results in refractory or relapsed PMBCL.
How do I treat dMMR/MSI gastro-oesophageal adenocarcinoma in 2025? A position paper from the EORTC-GITCG gastro-esophageal task force.
de la Fouchardière C, Cammarota A, Svrcek M … +8 more , Alsina M, Fleitas-Kanonnikoff T, Lordick Obermannová R, Wagner AD, Yap Wei Ting D, Enea D, Petrillo A, Smyth EC
Cancer Treat Rev · 2025 Mar · PMID 39933210 · Publisher ↗
In less than a decade, immune checkpoint inhibitors (ICIs) have transformed the management of mismatch repair-deficient (dMMR) and microsatellite instability-high (MSI) cancers. However, beyond colorectal cancer (CRC), m...
In less than a decade, immune checkpoint inhibitors (ICIs) have transformed the management of mismatch repair-deficient (dMMR) and microsatellite instability-high (MSI) cancers. However, beyond colorectal cancer (CRC), much of the evidence is mostly derived from non-randomized phase II studies or post-hoc analyses of broader clinical trials. dMMR/MSI tumours represent a specific subgroup of gastro-esophageal adenocarcinomas (GEA), accounting for approximately 9 % of cases, with a higher prevalence in early-stage compared to advanced-stage disease and older female patients. These tumours are predominantly sporadic, often linked to MLH1 promoter methylation, and rarely exhibit HER2 overexpression/ERBB2 amplification or other oncogenic drivers. The treatment landscape for early stage dMMR/MSI GEA is likely to change substantially soon, as ICIs have shown high pathological complete response (pCR) rates in small phase II trials, raising questions on optimisation of neoadjuvant therapy, and paving the way for organ preservation. The standard of treatment for untreated patients with advanced dMMR/MSI GEA is chemotherapy + ICI irrespectively of PDL-1 status. However, the role of chemotherapy-free regimen consisting of CTLA-4 plus PD-1 inhibitors remains undetermined. This review addresses these and other emerging questions, offering expert opinions and insights into the future therapeutic landscape for dMMR/MSI GEA.
Diagnosis and management of bispecific T cell-engaging antibody toxicity: A primer for emergency physicians.
Wattana MK, Rowland J, Qdaisat A … +7 more , Levavi H, Anagnostou T, Sanchez L, Friedlander P, Rohs N, Lipe DN, Richter J
Cancer Treat Rev · 2025 Mar · PMID 39913958 · Publisher ↗
BACKGROUND: T-cell-engaging bispecific antibodies (BsAbs) are a newer type of immunotherapy designed to boost T-cell cytotoxicity. They are increasingly used in cancer treatment, with drugs currently being tested and aut...
BACKGROUND: T-cell-engaging bispecific antibodies (BsAbs) are a newer type of immunotherapy designed to boost T-cell cytotoxicity. They are increasingly used in cancer treatment, with drugs currently being tested and authorized for treating both liquid and solid tumors. It's becoming more likely that emergency physicians and other acute care practitioners will treat patients experiencing adverse events related to bispecific antibodies, as these drugs are regularly given in the outpatient setting. Currently, BsAb-associated side effects are not routinely taught to Emergency Medicine residents, and a paucity of literature exists to guide currently practicing Emergency Medicine physicians and other acute care practitioners about these medications. OBJECTIVE OF THE REVIEW: This review was written by emergency medicine physicians in collaboration with oncologists who routinely administer BsAbs to provide guidelines and an overview on diagnosis, treatment, and management strategies for adverse events related to bispecific antibodies. DISCUSSION: Side effects related to BsAbs require a multidisciplinary treatment approach ideally with oncologists notified early when an adverse event is suspected. Symptom presentation is subtle with BsAb toxicity and the main adverse events to consider working up are cytokine release syndrome, immune effector cell neurotoxicity, and infection. The article also discusses unique side effects specific to FDA-approved drugs to treat leukemia, multiple myeloma, lymphoma, lung cancer, and melanoma given that this drug class has heterogeneous receptor-specific side effects.
Challenges and perspectives in the management of BRAF-mutated metastatic melanoma: Systemic treatment sequencing and brain metastases.
Martin-Liberal J, Márquez-Rodas I, Cerezuela-Fuentes P … +9 more , Soria A, Garicano F, Medina J, García Galindo R, Oramas J, Luis Manzano J, Delgado M, Valdivia J, Sanchez P
Cancer Treat Rev · 2025 Feb · PMID 39879863 · Publisher ↗
The global incidence of metastatic melanoma with BRAF mutations, characterized by aggressive behavior and poor prognosis, is rising. Recent treatment advances, including immune checkpoint inhibitors (ICI) and targeted th...
The global incidence of metastatic melanoma with BRAF mutations, characterized by aggressive behavior and poor prognosis, is rising. Recent treatment advances, including immune checkpoint inhibitors (ICI) and targeted therapies (TT) such as BRAF and MEK inhibitors, have significantly enhanced patient outcomes. Although guidelines recommend sequencing strategies, real-world implementation can be influenced by clinical scenarios. This article highlights the importance of tailored treatment strategies, emphasizing that the decision to initiate immunotherapy (IT) or TT hinges on multiple factors, including tumor burden, LDH levels, presence of brain metastases, and patient symptomatic status. Managing brain metastases also poses a challenge, as these patients are typically excluded from pivotal clinical trials. While insights from phase II studies provide some guidance, there is a critical need for more quality data to inform comprehensive recommendations. Furthermore, although triple therapy combining IT and TT was initially thought to be promising, it has failed to clearly demonstrate benefit over current treatments. For all these reasons, there is an imperative need for further research on biomarkers and predictive factors, as well as real-world studies, that will help tailor treatment strategies across diverse patient subsets, thereby refining therapeutic approaches for BRAF-mutated metastatic melanoma.
Safety of topical estrogen therapy during adjuvant endocrine treatment among patients with breast cancer: A meta-analysis based expert panel discussion.
Kastora SL, Pantiora E, Hong YH … +14 more , Veeramani M, Azim HA, Chakrabarti R, Geisler J, Knoop A, Lambertini M, Linderholm B, Meattini I, Partridge AH, Vaz-Luis I, Vorburger D, Yongue G, Karakatsanis A, Valachis A
Cancer Treat Rev · 2025 Feb · PMID 39854791 · Publisher ↗
IMPORTANCE: Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symp...
IMPORTANCE: Endocrine treatments, such as Tamoxifen (TAM) and/or Aromatase inhibitors (AI), are the adjuvant therapy of choice for hormone-receptor positive breast cancer. These agents are associated with menopausal symptoms, adversely affecting drug compliance. Topical estrogen (TE) has been proposed for symptom management, given its' local application and presumed reduced bioavailability, however its oncological safety remains uncertain. OBJECTIVE: The present systematic review, meta-analysis and expert panel review aimed to evaluate the strength of the available evidence on the risk of recurrence and mortality when TE is utilised in congruence with TAM or AI treatment, among BC survivors. DATA SOURCES: Six databases and two prospective registers, were interrogated from inception to January 3rd, 2024. Search terms were Breast cancer AND Hormone replacement therapy AND topical/vaginal oestrogen AND recurrence/mortality. STUDY SELECTION: All study designs reporting the use vs. non-use of TE in breast cancer survivors receiving adjuvant endocrine treatment were included. Six observational studies were deemed eligible for inclusion. DATA EXTRACTION AND SYNTHESIS: Sources of heterogeneity were explored using subgroup analysis by risk of bias, median follow-up period, node positivity and menopausal status. Trial sequential analysis was performed to quantify outcome reliability. A global expert panel was called to deliberate on the data, pinpoint areas of limited understanding, and determine the most important areas for future research. MAIN OUTCOMES AND MEASURES: Risk ratio effect sizes (RR) and corresponding 95 % Confidence Intervals (CI) of breast cancer recurrence and mortality in survivors on endocrine treatment (TAM and/or AI) exposed to TE were reported. Expert panel appraisal of meta-analysis evidence with definition of current knowledge gaps and future research aims. RESULTS: In 38 050 female patients receiving adjuvant endocrine treatment, of whom 1805 had been exposed to TE, TE exposure of those on AI, did not increase all-cause mortality (RR 0.99 [95 %CI 0.58, 1.69], I = 81 %, P = 0.96; moderate GRADE certainty). However, such exposure may convey an increased risk of recurrence (RR 2.51 [95 % CI 1.10, 5.72], I = 9 %, P = 0.03; low-GRADE certainty). Exposure to TE during TAM did not increase either recurrence risk or all-cause mortality. Clinical factors such as lymph node positivity at the time of diagnosis and menopausal status and follow-up time appeared to be significant confounders. CONCLUSIONS AND RELEVANCE: The use of TE does not appear to increase either recurrence or mortality risk among BC survivors treated with TAM. An increased recurrence risk, without an increase in mortality, cannot be ruled out when TE is used during AI.
Claudins as diagnostic tools and therapeutic targets-Glimpse of the horizon.
Sugiyama K, Chau I
Cancer Treat Rev · 2025 Feb · PMID 39847825 · Publisher ↗
Claudins (CLDNs) play a crucial and indispensable role as fundamental components within the structure of tight junctions. Due to the distinct and unique distribution pattern exhibited by CLDNs in both normal and malignan...
Claudins (CLDNs) play a crucial and indispensable role as fundamental components within the structure of tight junctions. Due to the distinct and unique distribution pattern exhibited by CLDNs in both normal and malignant tissues, these proteins have garnered significant attention as pivotal targets for systemic anti-cancer therapy and as noteworthy diagnostic markers. This review provides a comprehensive and detailed elucidation of the fundamental understanding surrounding CLDNs, their intricate expression patterns, the potential role they play in cancer diagnosis and therapeutic potentials; all encapsulated within a succinct summary of the cutting-edge advancements and the information derived from various clinical trials.
Dendritic cells in triple-negative breast cancer: From pathophysiology to therapeutic applications.
Sebastião AI, Simões G, Oliveira F … +6 more , Mateus D, Falcão A, Carrascal MA, Gomes C, Neves B, Cruz MT
Cancer Treat Rev · 2025 Feb · PMID 39837068 · Publisher ↗
Breast cancer is the second most commonly diagnosed cancer in women and the fifth leading cause of cancer-related deaths worldwide. It is a highly heterogeneous disease, consisting of multiple subtypes that vary signific...
Breast cancer is the second most commonly diagnosed cancer in women and the fifth leading cause of cancer-related deaths worldwide. It is a highly heterogeneous disease, consisting of multiple subtypes that vary significantly in clinical characteristics and survival outcomes. Triple-negative breast cancer (TNBC) is a particularly aggressive and challenging subtype of breast cancer. Several immunotherapeutic approaches have been tested in patients with TNBC to improve disease outcomes, including the administration of dendritic cell (DC)-based vaccines. DCs are a heterogeneous cell population that play a crucial role in bridging the innate and adaptive immune systems. Therefore, DCs have been increasingly used in cancer vaccines due to their ability to prime and boost antigen specific T-cell immune responses. This review aims to provide a comprehensive overview of TNBC, including potential targets and pharmacological strategies, as well as an overview of DCs and their relevance in TNBC. In addition, we review ongoing clinical trials and shed light on the evolving landscape of DC-based immunotherapy for TNBC.
Therapeutic strategies and landscape of metaplastic breast cancer.
Dai P, Song T, Liu J … +4 more , He Z, Wang X, Hu R, Yang J
Cancer Treat Rev · 2025 Feb · PMID 39827533 · Publisher ↗
Metaplastic breast cancer is a rare and heterogeneous subtype of breast cancer, associated with a poor prognosis. Its distinct biological behavior and morphological features contribute to resistance to standard treatment...
Metaplastic breast cancer is a rare and heterogeneous subtype of breast cancer, associated with a poor prognosis. Its distinct biological behavior and morphological features contribute to resistance to standard treatment regimens. Hitherto, the optimal therapeutic strategy for metaplastic breast cancer remains underexplored. Herein, we review the literature on the treatment of metaplastic breast cancer, summarizing current local and systemic therapies, and discuss potential therapeutic targets and novel strategies based on its pathological and molecular characteristics. Targeted therapy and immunotherapy may provide more personalized treatment options, with the potential to improve the prognosis of this disease.
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