Current Treatment Options in Oncology最新文献

Opinion statement: Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade mesenchymal neoplasm that arises in the dermis and subcutaneous tissue. Clinically, DFSP presents as a slow-growing cutaneous plaque or nodular mass that is often initially mistaken for a benign dermatological condition, such as a keloid, a dermatofibroma or morphea. Due to its local aggressiveness and proclivity for subclinical spread and recurrence, accurate diagnosis and complete surgical excision are critical. Although DFSP rarely metastasises, its morbidity primarily stems from locally invasive growth and potential disfigurement due to extensive resections. The pathognomonic COL1A1-PDGFB fusion, which can be detected using fluorescence in situ hybridisation (FISH) or reverse transcription polymerase chain reaction (RT-PCR), sustains autocrine PDGFRβ activation and can be used as a diagnostic marker and a target for the drug imatinib. Emerging genomic studies have revealed additional fusions, such as COL1A2-PDGFB and FBN1-CSAD, as well as mutations, such as CDKN2A/B deletions, that correlate with more aggressive, fibrosarcomatous (FS) variant. We reviewed the diagnostics of DFSP, including histopathology, immunohistochemistry (e.g. CD34, factor XIIIa, S100 and PRAME) as well as clinical presentation and recommended imaging modalities (e.g. ultrasound, MRI and PET/CT). To provide a better understanding of DFSP we discussed the molecular basis of DFSP, including the main genetic drivers and downstream signalling pathways, such as Ras-MAPK, PI3K-Akt and FGFR. Moreover, as there is no definitive staging system for DFSP, we proposed a novel one, integrating the presence of FS differentiation.

Opinion statement: Older adults with acute myeloid leukemia (AML) face disproportionately poor outcomes, driven by a combination of high-risk disease biology and functional vulnerabilities that are often overlooked by conventional oncology assessments. Geriatric assessment (GA) offers a multidimensional approach to uncover these impairments-spanning physical function, cognitive status, comorbidity burden, and emotional well-being-and provides critical information that independently predicts survival and treatment tolerance. Early studies demonstrate that GA can personalize treatment intensity decisions, inform supportive care interventions, and improve quality of life, yet its incorporation into routine AML care remains limited. Barriers to broader implementation include the need for streamlined workflows, clinician training, and large-scale validation. Future efforts should focus on integrating GA with biological markers of aging and disease to refine risk stratification, and leveraging digital tools and artificial intelligence to enhance feasibility and scalability. Ultimately, optimizing the management of older adults with AML will require a personalized, goal-concordant approach that combines GA-driven risk assessment with emerging therapeutic and supportive care strategies, ensuring that treatment intensity is matched to both disease biology and individual patient resilience.

Opinion statement: Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are among the most common adult soft tissue sarcoma (STS) subtypes. Due to their high genetic complexity, heterogeneity, and lack of specific genetic alterations, no consistent molecular targets for targeted therapy have been identified for UPS and MFS. Recently, immune checkpoint inhibition (ICI) has emerged as a promising treatment modality for UPS and MFS. However, the efficacy of ICI in UPS and MFS remains far lower than in other cancers such as melanoma. Strategies to increase the efficacy of ICI, including selecting patients based on putative biomarkers and combining ICI with chemotherapy, targeted therapies, and/or radiation therapy, are currently in clinical development. In this review, we first summarize the clinical characteristics of UPS and MFS, examining the tumor microenvironment (TME) and its effect on the efficacy of ICI. We then review putative biomarkers of ICI response and highlight clinical trials testing ICI in patients with UPS and MFS. Finally, we discuss other forms of immunotherapy for UPS and MFS currently under preclinical investigation. The combination of ICI plus radiation therapy appears to have benefit for patients with localized UPS and MFS. ICI should be considered for patients with advanced or unresectable UPS and MFS, especially those with potential biomarkers of response such as tertiary lymphoid structures (TLS). However, singular biomarkers such as TLS may prove inadequate to predict ICI response; more accurate prediction will likely require a panel of biomarkers including TLS, immune cell infiltration, PD-L1 expression, and other TME components.

Opinion statement: Novel strategies utilizing immune checkpoint inhibitors (ICIs) have emerged over the past several years and substantially changed the treatment landscape of advanced gastric cancer (GC). Based on the encouraging results achieved, numerous clinical studies have been conducted to identify the feasibility and efficacy of integrating ICIs into the perioperative treatment of locally advanced gastric and gastroesophageal junction cancer (GC/GEJC). Initial clinical trials have indicated that the addition of immunotherapy to chemotherapy, concurrent chemoradiotherapy, or chemotherapy combined with anti-angiogenic therapy in the perioperative setting significantly improves the pathological remission of patients, thereby promising to improve the prognosis. However, in the absence of strong evidence from long-term follow-up data, these approaches have yet to be entirely translated into clinical practice. Therefore, it is recommended that the aforementioned patients be prioritized for participation in clinical trials. In addition, based on the negative results of ATTRACTION-05, current evidence does not support the use of adjuvant immunotherapy in patients without neoadjuvant immunotherapy. For patients with dMMR/MSI-H disease, neoadjuvant immunotherapy has demonstrated excellent pCR rates, and the 2024 NCCN guidelines have recommended neoadjuvant or perioperative ICIs for these patients. In HER2-positive locally advanced GC/GEJC, neoadjuvant dual PD-1 and HER2 inhibition combined with chemotherapy has also shown promising prospects. However, the development of perioperative ICIs has also posed formidable therapeutic challenges. Given the high heterogeneity of GC, there is an urgent need to select patients likely to benefit from ICIs with precision through microenvironment analysis, molecular biomarker screening, and clinical subgroup analysis. In parallel, the benefits of ICIs in locally advanced GC/GEJC should be carefully weighed against their associated adverse effects and significant financial toxicity.

Opinion statement: Ovarian cancer, particularly high-grade serous carcinoma (HGSC), remains a leading cause of mortality in gynecologic oncology. Emerging research identifies serous tubal intraepithelial carcinoma (STIC) as a precursor lesion in many HGSC cases, highlighting its role in ovarian cancer pathogenesis and prevention. Management of STIC is challenging, as there is only limited data available to guide clinical decision-making. For average-risk women, opportunistic salpingectomy is increasingly being adopted during routine procedures such as hysterectomy or cesarean section. This intervention has demonstrated significant potential in reducing ovarian cancer incidence while maintaining safety and feasibility. For high-risk individuals, particularly BRCA mutation carriers, risk-reducing salpingo-oophorectomy (RRSO) remains the gold standard. RRSO significantly lowers ovarian cancer risk, though alternative approaches like salpingectomy alone or radical fimbriectomy are under investigation to preserve ovarian function in younger patients. To improve STIC detection, SEE-FIM pathology protocol is recommended when patients are undergoing risk-reducing surgery to prevent ovarian cancer, but challenges such as diagnostic variability and limited data persist. When STIC is detected incidentally, management varies based on risk factors and lesion characteristics. Genetic counseling and testing are essential when STIC is identified, as hereditary predisposition may guide further management. Surgical management is advised for cases of STIC with microinvasive carcinoma, but routine use of surgical management for STIC is not clearly defined in the literature. Bilateral oophorectomy is generally recommended when STIC is identified, and adnexal structures have not yet been removed. Chemotherapy is not recommended for treatment of STIC. Surveillance is suggested when STIC has been diagnosed, but there are no set guidelines as to the frequency and type of monitoring. Future directions include refining molecular profiling to predict progression and conducting randomized studies to establish evidence-based guidelines. Multidisciplinary collaboration is essential to optimize prevention and treatment, ultimately reducing HGSC incidence and improving patient outcomes.

Opinion statement: Pancreatic adenocarcinoma remains a leading cause of cancer-related mortality worldwide. Although surgery can be curable for a subset of patients, the five-year overall survival remains less than 15%. Despite extensive molecular characterization of pancreatic cancer, cytotoxic chemotherapy has served as the major component in therapeutic management. A major driver of pancreatic adenocarcinoma is mutations in KRAS, present in over 90% of cases. However, attempts to inhibit KRAS through upstream and downstream targets through the mitogen-activated protein kinase pathway have not been successful in the past. Despite this, multiple KRAS inhibitors have recently entered clinical trials and have shown promising results. These inhibitors have the potential to dramatically alter the landscape of treatment. In parallel, immunological approaches utilizing vaccines and bispecific antibodies are also in clinical development. Given these rapid new developments, the future of pancreatic cancer treatment will likely be determined by discovering the appropriate combinations of targeted and immune-based treatments.

Opinion statement: The ongoing challenge of addressing breast cancer, one of the most prevalent cancers and a principal cause of mortality among women globally, has reached a critical juncture with the advent of precision medicine and the promise of nanotechnology. As the scientific community's understanding of breast cancer's genomic landscape has deepened, it has become evident that a one-size-fits-all approach to treatment is obsolete. The evolution from rudimentary immunohistochemical classifications to intricate molecular profiling has ushered in an era where therapy is increasingly tailored to the individual's genetic makeup, environmental factors, and lifestyle choices. This shift towards personalized, biomarker-driven treatments not only aims to enhance prognosis but also to minimize adverse effects by meticulously matching therapy to the unique molecular characteristics of each tumor. The integration of nanotechnology, particularly through the deployment of nanoparticles for targeted drug delivery and nano-theranostics, represents a groundbreaking stride in oncological treatment. This convergence of precision medicine and nanotechnology in breast cancer care suggests a future where combination therapies and multifunctional approaches could potentially outsmart drug resistance and augment treatment efficacy. However, the path forward is fraught with challenges such as overcoming inherent tumor heterogeneity and improving the accessibility of cutting-edge treatments. The exploration of these innovative strategies in breast cancer therapeutics underscores the critical need for a multifaceted approach to cancer care, emphasizing the potential of these advances to revolutionize treatment paradigms and offer new hope to patients.

Opinion statement: Patients with advanced stage completely resected endometrial cancer represent a heterogeneous group and decision-making regarding adjuvant treatment for this patient population is complex. When considering this cohort of patients, factors such as histologic subtype and molecular classification impact decision-making on adjuvant therapy. Options include systemic chemotherapy with or without immunotherapy or HER2-targeted therapy, chemoradiotherapy and radiation alone. We recommend tailoring treatment for patients with advanced-stage, non-measurable endometrial cancer based on HER2 status, mismatch repair (MMR) proficiency, disease stage and histology. For HER2-positive cases, we recommend carboplatin, paclitaxel, and trastuzumab. For HER2-negative, MMR-proficient disease, Stage 3 patients we recommend that have stage IIIB or IIIC disease AND grade 1 or 2 endometrioid histology OR grade 3 endometrioid histology p53 wild-type, we recommend carboplatin and paclitaxel, with consideration of the addition of pelvic radiationFor patients with stage IIIA disease OR grade 3 p53 aberrant endometrioid OR non-endometrioid histology, we recommend carboplatin and paclitaxel, with consideration of brachytherapy for patients with uterine risk factors such as lymphovascular space invasion, cervical stromal involvement, or lower uterine segment involvement. For Stage 4 patients with Her2 negative, MMRp disease, we recommend carboplatin and paclitaxel, with optional brachytherapy. For HER2-negative, MMR-deficient disease, the recommended regimen includes carboplatin, paclitaxel, and immunotherapy, with consideration of brachytherapy for patients with the uterine risk factors listed above.

Opinion statement: The integration of next-generation sequencing (NGS) and advanced cytogenetic diagnostics into routine clinical practice is reshaping frontline treatment of acute myeloid leukemia (AML) in both fit and unfit patients. Molecular profiling now enables personalized treatment strategies, particularly for patients harboring mutations in FLT3, IDH1, IDH2, KMT2A, and NPM1. Small molecule inhibitors, first reserved for relapsed/refractory disease, are increasingly used in the upfront setting. However, universal NGS testing at diagnosis is critical to identify eligible patients for these targeted therapies. In patients lacking actionable mutations, treatment can still be refined using karyotypic abnormalities or high-risk features suggestive of antecedent MDS. In our practice, we continue to use 7 + 3 induction for fit patients, adding midostaurin or quizartinib for FLT3-mutated AML, or gemtuzumab ozogamicin for core binding factor (CBF) AML expressing CD33. For patients with therapy-related AML or AML with myelodysplasia-related changes, CPX-351 is our standard induction approach. For unfit patients, we generally offer hypomethylating agents with venetoclax. In the presence of IDH1 mutations, we consider azacitidine combined with ivosidenib. If venetoclax is contraindicated or not tolerated, targeted therapies such as gilteritinib, ivosidenib, or enasidenib may be appropriate based on mutation profile. However, we try to identify clinical trials for all our patients at diagnosis. One of the more exciting recent developments is the emergence of menin inhibitors for patients with KMT2A rearrangements or NPM1 mutations. While several agents have received FDA approval or breakthrough status in the relapsed/refractory setting, they are now being actively studied as frontline options with promising results. When feasible, clinical trial enrollment should be considered for newly diagnosed patients with these alterations. As the therapeutic landscape for AML continues to evolve, timely molecular characterization is more essential than ever to optimize outcomes and select the most appropriate frontline strategy.

Opinion statement: PARP inhibitors (PARPi) are increasingly vital in treating, particularly in individuals exhibiting homologous recombination deficiency (HRD), harnessing synthetic lethality to target tumor cells. However, PARPi resistance severely restricts their sustained efficacy, posing a significant clinical obstacle requiring a detailed exploration of its mechanisms and solutions. This review elucidates the underlying mechanisms of PARPi resistance, assesses biomarker-driven predictive tools, and explores novel strategies to improve therapeutic outcomes. This review critically assesses biomarker-driven strategies for resistance prediction, such as genomic profiling, functional assays, dynamic circulating tumor DNA (ctDNA) monitoring, and emerging markers, to refine patient stratification. Moreover, this review systematically dissects PARPi resistance, including genomic alterations, homologous recombination (HR) restoration, replication fork stabilization, enhanced drug efflux, reduced PARP1 trapping, and microenvironmental influences. In addition, therapeutic tactics to prevent or overcome resistance are evaluated, encompassing sequential PARPi use, combinations with chemotherapy, immunotherapy, antiangiogenic agents, and DNA damage response (DDR) inhibitors, alongside innovative approaches like antibody-drug conjugates (ADCs). Bridging mechanistic and clinical perspectives, this review promotes a multidisciplinary approach to optimize PARPi-based treatments, addressing current challenges in ovarian cancer management.