Esophageal cancer remains one of the most lethal malignancies worldwide, with particularly poor outcomes following disease progression after first-line chemoimmunotherapy. Antibody-drug conjugates (ADCs) have emerged as a transformative therapeutic class that combines the targeting precision of monoclonal antibodies with potent cytotoxic payloads, enabling selective tumor cell killing while minimizing off-target toxicity. In the management of advanced esophageal cancer, I advocate for the integration of ADCs as a therapeutic option following progression on first-line chemoimmunotherapy. For patients with human epidermal growth factor receptor 2 (HER2)-positive gastroesophageal junction adenocarcinoma, trastuzumab deruxtecan is my preferred choice based on its superior overall survival benefit and robust bystander killing effect, which also confers activity in HER2-low tumors. For HER2-negative gastroesophageal adenocarcinoma, trophoblast cell-surface antigen 2 represents a promising target given its high prevalence of moderate to strong expression in nearly 80
Lung cancer remains the leading cause of cancer-related mortality. The 5-year survival rate for advanced non-small cell lung cancer (NSCLC) is only 20
Pancreatic cancer represents a malignant tumor of the digestive system with an inferior clinical prognosis, primarily attributable to the challenges in early diagnosis that preclude surgery-based treatment for most patients. Furthermore, the high postoperative recurrence rate significantly limits long-term survival in surgical candidates. Among patients experiencing recurrence after pancreatic cancer resection, local recurrence emerges as one of the most prevalent patterns. Early detection remains equally critical for recurrent cases, as selected patients undergoing potentially curative therapy for localized recurrence demonstrate that they can still extend post-recurrence survival. This comprehensive review synthesizes current evidence regarding the pathogenesis, risk determinants, diagnostic approaches, therapeutic interventions, and preventive measures for local recurrence following pancreatic cancer surgery. Emphasis is placed on analyzing the potential etiopathogenetic mechanisms and risk determinants for postoperative local recurrence, including tumor biology characteristics, tumor microenvironment interactions, and clinicopathological influences, providing foundations for preventive strategies. Emerging diagnostic modalities, particularly advanced imaging, and histopathological techniques, enhance early detection of locoregional recurrence. The review further examines evolving treatment paradigms encompassing precision radiotherapy, targeted systemic therapies, and innovative immunotherapeutic approaches for recurrent disease management. By integrating multidisciplinary perspectives, this work aims to inform optimized preventive approaches, surveillance and diagnostic protocols, and advance personalized management strategies for postoperative local recurrence in patients with pancreatic cancer.
Troponins are an integral part of the diagnosis of acute coronary syndromes in cardiology. It is also useful in many other acute cardiological conditions, such as acute pulmonary embolism. In cardio-oncology, it is part of the definition of either cancer disease or cancer therapy related cardiovascular toxicity. Change in troponin value is one of the diagnostic criteria for mild and moderate cancer therapy related cardiac dysfunction. Diagnosis of myocarditis is also based on troponin elevation. However, an ideal cut-off points for precise diagnostic value and indication for cardiology treatment have not yet been defined.It is still difficult to make therapeutic decisions in cardio-oncology about the initiation, intensification or modification of cardiac therapy based on the dynamics of troponin changes.
With improved cancer survival, cancer therapy-related cardiovascular toxicity has emerged as a major non-cancer cause of morbidity and mortality in cancer survivors. The marked heterogeneity of CTR-CVT cannot be fully explained by single-pathway models, underscoring the need for a systems-level framework centered on regulated cell death networks. This review integrates recent advances to propose an RCD–cellular process interaction network in CTR-CVT, focusing on apoptosis, ferroptosis, pyroptosis, necroptosis, and selected emerging RCD modalities. We emphasize the mitochondrial dynamics–autophagic flux–metabolic reprogramming axis as a central regulatory module that shapes RCD activation, pathway crosstalk, and cell fate under anticancer drug stress. We also incorporate the reverse cardio-oncology concept to discuss potential bidirectional interactions between myocardial injury and tumor progression, and to identify therapeutic targets that enable cardioprotection while preserving antitumor efficacy. Building on this framework, we outline a translational strategy that integrates mechanism-based risk stratification, biomarker-guided early warning, and targeted cardioprotection, with reference to the 2022 ESC Cardio-Oncology Guidelines and representative clinical scenarios including breast cancer, hematological malignancies, and lung cancer. This mechanism-oriented approach may support biomarker discovery, mechanism-matched intervention, and the development of precision cardio-oncology. Future studies should prioritize mitochondrial quality control and metabolic plasticity as therapeutic entry points to reduce cardiovascular risk without compromising cancer treatment outcomes.
Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although advances in early diagnosis and conventional therapies have significantly improved the prognosis in many cases, certain aggressive subtypes such as triple-negative breast cancer continue to pose major clinical challenges due to the absence of specific therapeutic targets. Therefore, we believe that exploring novel strategies for the development and application of immunotherapy may change the paradigm for this type of tumor. Immunotherapy aims to activate the patient’s own immune system to recognize and eliminate tumor cells more effectively and selectively, improving immunological memory. Based on a structured review of scientific literature and therapeutic clinical trials published in the main scientific databases, including studies of different clinical phases and stages of the disease, from early-stage to metastatic breast cancer, we conclude that immune checkpoint inhibitors, especially when combined with chemotherapy and administered to patients with positive biomarkers, such as PD-L1 expression, provide significant clinical benefits. In addition, therapeutic vaccines continue to be studied as a promising approach to preventing relapses in high-risk patients when combined with other immunotherapy agents. This represents a major advance in the treatment of the most aggressive subtypes of breast cancer, positioning immunotherapy as one of the most promising treatments. Immune Checkpoint Inhibitors and Therapeutic Vaccines has emerged as treatment for breast cancer The large number of clinical trials conducted using different strategies emphasizes their potential The use of Immune Checkpoint Inhibitors both alone and in combination has shown promising results in clinical trials Therapeutic vaccines represent a developmental strategy aimed at stimulating long-lasting immune memory to help prevent recurrence Despite major advances, immunotherapy still has limitations to overcome
Anaplastic thyroid carcinoma (ATC) is a highly aggressive malignancy characterized by rapid progression, restricted therapeutic options, and dismal prognosis. Conventional therapeutic modalities demonstrate limited efficacy, especially for unresectable or metastatic cases. Recent advancements in molecular profiling have revolutionized ATC management, facilitating the development of novel targeted therapies, immunotherapies, and multimodal regimens. Growing clinical evidence indicates these innovative approaches may enhance locoregional control, increase surgical candidacy in select patients, and extend overall survival. Incorporating molecular-guided therapies into multidisciplinary care is fundamentally transforming ATC management. Nevertheless, therapeutic resistance, intratumoral heterogeneity, and the paucity of large-scale prospective trials remain major obstacles. Future efforts should focus on optimizing combinatorial strategies and developing robust biomarker-driven algorithms to improve clinical outcomes in ATC.
The field of immunotherapy for unresectable soft tissue sarcomas (STS) is transitioning from a one-size-fits-all approach toward a precision immuno-oncology paradigm. The pronounced immunological heterogeneity among histological subtypes and the limited predictive capacity of traditional classification underscore the imperative for immune-based stratification. Approximately 20
As survival among reproductive-age patients with breast cancer continues to improve with modern therapies, concerns regarding fertility preservation, gonadotoxicity, and pregnancy safety have become increasingly prominent. Fertility considerations are well-recognized contributors to treatment refusal and premature discontinuation, therefore, oncofertility counselling should be initiated at diagnosis and integrated into therapeutic planning. Prompt referral for fertility preservation is essential for patients who may wish to conceive, without compromising oncologic outcomes. Systemic therapy selection should remain driven by tumour biology and recurrence risk; however, when clinically equivalent regimens are available, those with lower gonadotoxic potential are preferred. Cytotoxic chemotherapy is the main determinant of permanent ovarian insufficiency, and temporary ovarian suppression during chemotherapy should be routinely considered in appropriate candidates. Endocrine therapy is not associated with irreversible ovarian damage, but its long duration necessitates individualized planning for pregnancy, including supervised treatment interruption in selected low-risk patients. HER2-monoclonal antibodies should be delivered according to standard indications, as it does not appear to confer substantial additional ovarian toxicity beyond chemotherapy; however, pregnancy must be avoided during treatment. For antibody–drug conjugates, PARP inhibitors, and CDK 4 and 6 inhibitors, the absence of prospective human fertility data supports a precautionary approach, including pre-treatment fertility preservation, effective contraception during therapy, and adherence to recommended washout periods. Given the substantial gaps in clinical evidence, transparent communication of uncertainty is essential. The integration of standardized reproductive endpoints into clinical trials, alongside the development of predictive tools is critical to support evidence-based counselling and optimize long-term survivorship outcomes.
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment outcomes of patients with hematologic malignancies, including B-cell acute lymphoblastic leukemia (B-ALL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). However, issues such as antigen escape, T-cell exhaustion, and the limited efficacy of CAR-T cells in acute myeloid leukemia (AML) and T-cell leukemias still persist. This review aims to summarize human trials and achievements from 2015 with a focus on the innovations within the last two years. We discuss strategies to overcome resistance, including multi-target CARs, next-generation constructs, and combination strategies to treat resistant cancers. We also explore the ways to increase safety and access, including allogeneic CAR-T options. In this article, we propose CRISPR-enhanced CARs and synthetic biology-based allogeneic systems to enhance the efficacy and accessibility of CAR-T therapy with the aim of moving the field of oncology towards durable cures.
Immune checkpoint inhibitors have reshaped the therapeutic landscape of hepatocellular carcinoma by restoring T cell–mediated antitumor immunity. However, the clinical benefit of monotherapy remains limited, highlighting the need for improved patient stratification and more effective treatment strategies. HBV-related hepatocellular carcinoma (HBV-HCC) is a major etiological subtype characterized by a chronically immunosuppressive tumor microenvironment driven by persistent viral antigen exposure and immune exhaustion. We believe that patients with HBV-HCC may be more suitable for immunotherapy, especially treatment with immune checkpoint inhibitors. A deeper understanding of the expression patterns of inhibitory checkpoint and costimulatory molecules, along with the identification of predictive biomarkers and the development of effective combination immunotherapies is essential for improving clinical outcomes. From a safety perspective, hepatitis B virus reactivation is generally manageable when appropriate antiviral therapy is administered concurrently with immunotherapy. Consequently, patients with HBV-HCC should not be excluded from treatment with immune checkpoint inhibitors. We anticipate that combination strategies, including multi-target immune checkpoint blockade, combinations with other immunotherapeutic approaches, and microbiome-based therapy, will further enhance therapeutic efficacy in HBV-HCC. Combination immune checkpoint therapy may enhance antitumor responses and potentially contribute to better control of viral activity.
Hemithorax irradiation (HT‑RT) is a cornerstone multimodal treatment for high‑risk chest wall bone and soft tissue sarcomas, particularly Ewing sarcoma in children and young adults. Current non‑randomized evidence consistently shows HT‑RT reduces systemic relapse—especially lung metastases—without compromising local control or causing unmanageable acute toxicities, and modern techniques (IMRT, VMAT, proton therapy) further improve its therapeutic ratio by lowering late toxicity. Major gaps remain: no prospective randomized controlled trials (RCTs) confirm independent efficacy, the biological mechanisms are unclear, and long‑term pulmonary function and survivorship data in children are insufficient. Future research must prioritize prospective RCTs, pediatric‑specific dose constraints, advanced technique validation, and mechanistic studies to refine patient selection and optimize outcomes for this high‑risk population. Clinical Trial Number: Not applicable.
Solitary fibrous tumor (SFT) is an exceedingly rare mesenchymal neoplasm classified as a soft tissue sarcoma (STS). While historically considered indolent, up to 50
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor. Although patient survival has been significantly improved by immune checkpoint inhibitors combined with chemotherapy, three major unmet needs remain in SCLC management. First, while prophylactic cranial irradiation (PCI) can reduce the risk of brain metastases, its neurotoxicity limits its use, particularly in elderly patients or those with neurological deficits. Whole-brain radiotherapy (WBRT) remains the primary approach for brain metastases, and hippocampal-avoidance WBRT (HA-WBRT) combined with neuroprotective agents can significantly reduce cognitive risks. Stereotactic radiosurgery (SRS) has shown survival benefits and less cognitive damage for patients with up to 10 brain metastatic lesions. Emerging therapies, such as antibody-drug conjugates targeting B7-H3/DLL3 (I-Dxd, ZL-1310) and bispecific antibody tarlatamab, have demonstrated intracranial response rates of 62.5
Cancer pain is common, heterogeneous, and multidimensional. The management of cancer pain is evolving toward a personalized, mechanism-informed, and multimodal paradigm. In my practice, systematic pain assessment is performed early, and individualized analgesic therapy is initiated promptly rather than deferred until tumor-directed therapy achieves measurable effects. Opioids remain essential but are limited by toxicity, tolerance, and incomplete control of mixed nociceptive-neuropathic mechanisms. Careful agent selection, dose titration, proactive management of constipation and neurotoxicity, and early consideration of opioid rotation are essential to sustain efficacy and safety. Evidence questions routine acetaminophen add-on to strong opioids and supports individualized risk stratification when using nonsteroidal anti-inflammatory drugs (NSAIDs). For neuropathic and treatment-related pain, gabapentinoids and duloxetine remain key adjuvants. Emerging options, including cannabinoids, novel gabapentinoids (mirogabalin and criligabalin), anti-nerve growth factor (NGF) antibodies, and transient receptor potential vanilloid 1 (TRPV1)-targeted therapies (intrathecal resiniferatoxin and high-concentration capsaicin patches), show variable efficacy and require further evaluation before routine use. For refractory pain, neurolytic blocks, intrathecal drug delivery, and neuromodulation may provide meaningful opioid-sparing analgesia in selected patients. These strategies can provide meaningful analgesia and reduce systemic opioid exposure. Nonpharmacologic modalities, including cognitive-behavioral therapy, mindfulness-based interventions, exercise, acupuncture, and transcutaneous electrical nerve stimulation, should be incorporated whenever feasible to reduce symptom burden, improve physical function, and support patient coping and overall well-being. This approach ensures that pharmacologic and nonpharmacologic strategies are applied in an integrated, patient-centered manner. Ultimately, optimal cancer pain management requires coordinated multidisciplinary care, shared decision-making, and ongoing reassessment to align analgesic strategies with disease trajectory, patient goals, and quality of life.
The therapeutic landscape of GIST has evolved considerably with the widespread use of tyrosine kinase inhibitors and improved molecular characterization. For localized disease, complete surgical resection remains the primary treatment strategy, while TKI therapy is indicated for unresectable, metastatic, or high-risk tumors and as adjuvant treatment in selected patients. In this setting, imaging is fundamental to treatment selection and longitudinal management. In our practice, contrast-enhanced CT is the first-line modality for initial staging and assessment of resectability. Imaging findings guide decisions regarding upfront surgery versus neoadjuvant TKI therapy, particularly in large or anatomically challenging tumors where downsizing may facilitate organ-preserving resection. During systemic therapy, we rely on CT for routine monitoring but recognize that size criteria alone may underestimate early response. We therefore integrate MRI or FDG PET/CT selectively when treatment response is unclear or early resistance is suspected. Postoperatively, surveillance strategies are tailored according to recurrence risk and adjuvant therapy status. High-risk patients undergo closer imaging follow-up, whereas surveillance intensity may be reduced in low-risk cases to limit cumulative radiation exposure. Ultimately, careful integration of imaging with clinical and molecular factors enables more individualized and stage-appropriate management of GIST.
Opinion statement We focus our second-line treatment strategy on biomarker-defined resistance mechanisms that emerge after progression on CDK4/6 inhibitors. In our view, ESR1 mutation–mediated resistance constitutes a biologically distinct phenotype of endocrine resistance rather than a simple treatment escape. Therefore, in patients with ESR1-mutated tumors, we strongly favor incorporating next-generation oral selective estrogen receptor degraders (SERDs), given their targeted mechanism, favorable tolerability, and efficacy following CDK4/6 inhibition. For tumors harboring alterations in the PIK3CA–AKT–PTEN pathway, treatment selection is similarly biomarker driven. In patients with PIK3CA mutations, fulvestrant combined with alpelisib remains an effective option, though tolerability concerns often influence long-term adherence; accordingly, we increasingly prefer fulvestrant with capivasertib due to its activity across PIK3CA, AKT1, and PTEN alterations and its more manageable safety profile. When patients exhibit rapid progression, endocrine-independent biology, or aggressive visceral disease, we transition early to antibody–drug conjugates such as trastuzumab deruxtecan or sacituzumab govitecan, which demonstrate superior outcomes compared with conventional chemotherapy in appropriately selected cases. Overall, an individualized, biomarker-driven approach remains central to optimizing therapeutic sequencing in advanced HR+ breast cancer.
Opinion statement Mucosal melanoma (MM) represents a rare malignancy in Caucasian populations but constitutes one of the predominant melanoma subtypes among non-Caucasian ethnic groups. Due to its anatomic occult nature, a significant proportion of patients with MM present with advanced-stage disease at diagnosis. Characterized by distinct genomic profiles and an immunosuppressive tumor microenvironment, MM exhibits suboptimal responses to current targeted drugs and immune checkpoint inhibitors (ICIs). Combination immunotherapy can overcome immune evasion by enhancing the infiltration of tumor-specific antigen-reactive T lymphocytes, thereby exhibiting potentiated anti-tumor activity. However, the rarity of MM has posed significant barriers to better understanding immunotherapy resistance mechanisms and investigating novel therapies. Consequently, there is a critical unmet need for establishing standardized treatment guidelines to improve survival outcomes in advanced MM. This article comprehensively reviews current status in the treatment of advanced MM. It also discusses potential future directions for treatment based on recent advances from clinical trials and basic research.
