OncoTargets and therapy最新文献

[This retracts the article DOI: 10.2147/OTT.S289922.].

Purpose: Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is the standard treatment for patients with non-small cell lung cancer harboring EGFR mutations. Although the frequency of osimertinib-induced interstitial lung disease (osi-ILD) is high, the optimal cancer treatment after osi-ILD has not been established. This time, we focused on the safety and efficacy of gefitinib following osi-ILD.

Case presentation: We experienced six cases (five women and one man; median age: 74 years) in which gefitinib was administered after osi-ILD. All six cases had grade 2 or higher osi-ILD and required steroid treatment. The computed tomography imaging pattern of osi-ILD revealed organizing pneumonia in three cases, diffuse alveolar damage in two cases, and hypersensitivity pneumonia in one case. Eastern Cooperative Oncology Group performance status was 1 in four cases, 2 in one case, and 3 in one case. EGFR mutation status was exon 19 deletion in two cases and exon 21 L858R in four cases. Only one patient experienced recurrence of ILD after receiving gefitinib. The best response to gefitinib was partial response in two cases and stable disease in three cases; one case was not evaluable. The median progression-free survival after treatment with gefitinib was 190 days (95% confidence interval: 33-328).

Conclusion: The treatment with gefitinib after the development of osi-ILD was safe and effective. Gefitinib may be a promising option for patients who recovered from severe osi-ILD.

Recombinant cytokine products have emerged as a promising avenue in cancer therapy due to their capacity to modulate and enhance the immune response against tumors. However, their clinical application is significantly hindered by systemic toxicities already at low doses, thus preventing escalation to therapeutically active regimens. One promising approach to overcoming these limitations is using antibody-cytokine fusion proteins (also called immunocytokines). These biopharmaceuticals leverage the targeting specificity of antibodies to deliver cytokines directly to the tumor microenvironment, thereby reducing systemic exposure and enhancing the therapeutic index. This review comprehensively examines the development and potential of antibody-cytokine fusion proteins in cancer therapy. It explores the molecular characteristics that influence the performance of these fusion proteins, and it highlights key findings from preclinical and clinical studies, illustrating the potential of immunocytokines to improve treatment outcomes in cancer patients. Recent advancements in the field, such as novel engineering strategies and combination strategies to enhance the efficacy and safety of immunocytokines, are also discussed. These innovations offer new opportunities to optimize this class of biotherapeutics, making them a more viable and effective option for cancer treatment. As the field continues to evolve, understanding the critical factors that influence the performance of immunocytokines will be essential for successfully translating these therapies into clinical practice.

Rat sarcoma virus (RAS) GTPase is one of the most important drivers of non-small cell lung cancer (NSCLC). RAS has three different isoforms (Harvey rat sarcoma viral oncogene homolog [HRAS], Kirsten rat sarcoma viral oncogene homolog [KRAS] and Neuroblastoma ras viral oncogene homolog [NRAS]), of which KRAS is most commonly mutated in NSCLC. The mutated KRAS protein was historically thought to be "undruggable" until the development of KRAS^G12C inhibitors. In this review, from the aspect of brain metastasis, we aim to provide an overview of the advances in therapies that target KRAS^G12C, the limitations of the current treatments, and future prospects in patients with KRAS p.G12C mutant NSCLC.

Purpose: Treatment with immune-checkpoint inhibitors (ICIs) can be associated with a wide spectrum of immune-related adverse events (irAEs). Among irAEs, immune-mediated pneumonitis (im-PN) is a rare but potentially life-threatening side effect. TPrompt multidisciplinary diagnosis and effective management of im-PN may be essential to avoid severe complications and allowing resumation of therapy.

Patients and methods: We collected a case series of skin (melanoma, cutaneous squamous cell carcinoma-CSCC), lung, and mesothelioma cancer patients (pts), treated with ICI at the Center for Immuno-Oncology University Hospital of Siena, Italy, and diagnosed with im-PN. Clinical and radiologic data were thoroughly collected, as well as bronchoalveolar lavage (BAL) samples; im-PN was graded using CTCAE v. 5.0. Radiological patterns were reported according to the Fleischner Society classification.

Results: From January 2014 to February 2023, 1004 patients with melanoma (522), CSCC (42), lung (342) or mesothelioma (98) were treated with ICI (619 monotherapy; 385 combination). Among treated patients, 24 (2%) developed an im-PN and 58% were symptomatic. Im-PN were classified as grades G1 (10) and G2 (14). Prompt steroid treatment led to complete resolution of im-PN in 21 patients, with a median time to resolution of 14 weeks (range: 0.4-51). Twelve patients resumed ICI therapy once fully-recovered and 2 experienced a recurrence that completely resolved with steroids after resumption of treatment. Three radiologic patterns were identified: organizational pneumonia-like (67%), pulmonary eosinophilia (29%), and hypersensitivity pneumonitis (4%). Furthermore, BAL analysis performed in 8 (33%) patients showed an inflammatory lymphocytic infiltrate, predominantly consisting of foam cell-like macrophage infiltrates in 6 cases. Notably, transmission electron microscopy evaluation performed in 2 patients revealed a scenario suggestive of a drug-mediated toxicity.

Conclusion: Im-PN is a rare but challenging side effect of ICI therapy, with variable time of onset and with heterogeneous clinical and radiological presentations. A multidisciplinary assessment is mandatory to optimize the clinical management of im-PN.

[This retracts the article DOI: 10.2147/OTT.S183625.].

[This retracts the article DOI: 10.2147/OTT.S187670.].

[This retracts the article DOI: 10.2147/OTT.S226300.].

Background: As one of the most common types of primary bone sarcomas in adolescents and young adults, osteosarcoma has a high probability of local invasion and distant metastasis with a poor prognosis.

Case presentation: Here, we report the case of a 34-year-old patient with advanced metastatic osteosarcoma. Considering the high expression of PD-L1 and the inability of the patient to tolerate chemotherapy, anti-PD-1 antibody (sintilimab 200 mg, q3w) and anti-angiogenesis drug (anlotinib 8 mg D1-14, q3w) were administered. The metastatic lesions were treated with local radiotherapy. The patient obtained an 11.7-month-sustained remission period, and he also enjoyed a better quality of life.

Conclusion: This case demonstrates that sintilimab plus anlotinib may be a feasible treatment regimen for osteosarcoma patients.