TARGETED THERAPY AND IMMUNOTHERAPY IN COMBINED ANAPLASTIC AND PAPILLARY THYROID CARCINOMA WITH BRAF V600E MUTATION AND PD-L1 EXPRESSION: A CLINICAL CASE
Jul 2026· Eurasian Journal of Oncology and Radiology· pp. 136-145· 0 citations
TL;DR
Targeted therapy demonstrates temporary efficacy in anaplastic thyroid carcinoma; however, the development of resistance and the aggressive nature of the disease significantly limit long-term treatment outcomes.
Abstract
Relevance: Thyroid cancer is one of the most common malignant neoplasms of the endocrine system, demonstrating a steady increase in incidence worldwide. Particular attention among thyroid malignancies is drawn to anaplastic thyroid carcinoma (ATC), a rare but extremely aggressive form of the disease. Although it accounts for less than 2% of all thyroid cancers, anaplastic thyroid carcinoma is responsible for the majority of thyroid cancer-related mortality. ATC is characterized by a fulminant clinical course, rapid local progression, early metastasis, and marked resistance to conventional treatment methods, including surgery, radiotherapy, and chemotherapy. The median survival after diagnosis usually does not exceed 6-12 months, highlighting the poor prognosis of this disease. Thus, ATC remains one of the most challenging and unresolved problems in modern oncology, requiring further investigation, improvements in early diagnostic approaches, and the development of novel therapeutic strategies.The study aimed to evaluate the effectiveness of targeted therapy and immunotherapy in a patient with anaplastic thyroid cancer with the BRAFV600E mutation and PD-L1 expression.Materials and Methods: A clinical case of a 70-year-old female patient diagnosed with T4N1M1 stage IV anaplastic thyroid carcinoma is presented.Results: After surgical treatment and two courses of polychemotherapy, disease progression was observed with enlargement of metastatic lesions in the lungs and the appearance of subcutaneous dissemination. Molecular genetic testing revealed a BRAF V600E mutation; therefore, targeted therapy with a combination of dabrafenib and trametinib was initiated. During treatment, a short-term partial response lasting approximately 3 months was achieved, accompanied by a reduction in metastatic lesion size and improvement in clinical condition. Subsequently, further disease progression was noted. Given the high PD-L1 expression (TPS 100%), pembrolizumab was administered, but no clinical benefit was observed. The patient died shortly after the initiation of treatment. Targeted therapy provided only a temporary effect in the setting of aggressive disease progression.Conclusion: Targeted therapy demonstrates temporary efficacy in anaplastic thyroid carcinoma; however, the development of resistance and the aggressive nature of the disease significantly limit long-term treatment outcomes.
A patient with advanced BRAF-mutant ATC who recovered with a combination of the anti-PD1 nivolumab and the BRAF V600E targeted drug vemurafenib is shown, indicating further studies using biomarker-based gene- and immune-targeted agents, including in combination, are needed in ATC.
Noor Khalid, R. Kurzrock, Shumei Kato· npj Precision Oncology· 1 citation
ABSTRACT
Small cell lung cancer (SCLC) is an aggressive malignant tumor that mainly originates from pulmonary neuroendocrine cells and is characterized by rapid proliferation, high metastatic potential, and acquired therapeutic resistance. The therapeutic landscape for SCLC is largely confined to traditional modalities, such as surgery and chemoradiotherapy. However, 80-85% of patients are diagnosed with extensive-stage SCLC at initial presentation; surgical intervention and radiotherapy are often not applicable for these patients. Despite the initial favorable response of SCLC to chemotherapy, most patients develop resistance and experience rapid disease recurrence, leading to a poor prognosis. Historically, radiotherapy was the main mode of first-line treatment. With the advent of immune checkpoint inhibitors (ICIs) in recent years, the field of oncology has witnessed new therapeutic modalities and strategies. The combination of immunotherapy and chemotherapy has led to the development of extremely effective strategies for treating SCLC, significantly extending overall survival for a subset of patients. However, the overall clinical benefit remains limited; therefore, further optimization needs to be performed. This need has encouraged researchers to investigate novel therapeutic strategies. Antibody-drug conjugates targeting antigens, such as DLL3, B7-H3, and TROP2, are extremely effective in treating relapsed/refractory SCLC. In this review, the latest research advances in the carcinogenic, invasive, and drug-resistance mechanisms of SCLC have been summarized. We focused on the progress in the treatment modalities for SCLC and discussed future perspectives involving novel therapeutic combinations, assessment of new targets, and strategies to overcome treatment resistance.
Xiangwei Cheng, Weibin Lv, Linfeng Wu et al.· Journal of Cancer Research a...· 0 citations
Collectively, the advances are an indication of a transition to the personalized, mechanism-driven treatment strategies that would prolong the survivability of patients with advanced thyroid cancer, conquer resistance, and reduce systemic toxicity.
Tanmoy Sarkar, Ruhi Arisha, S. Sengupta et al.· Clinical and Translational O...· 0 citations
Progress in the understanding of ATC biology is highlighted, with a focus on driver genetic alterations, metabolic plasticity and microenvironmental interactions that underpin its exceptional aggressiveness, to provide a rationale for the design of multimodal therapeutic strategies urgently needed to improve outcomes for patients with ATC.
Anaplastic thyroid carcinoma (ATC) is a rare, highly aggressive thyroid malignancy associated with rapid progression, diagnostic complexity, and poor prognosis, particularly true when arising through dedifferentiation of pre-existing papillary thyroid carcinoma (PTC).
We present the case of a 63-year-old female with a history of papillary thyroid carcinoma (PTC) previously treated with total thyroidectomy and radioactive iodine ablation 10 years prior. She presented with a rapidly enlarging anterior neck mass, progressive dysphagia, hoarseness, and intermittent stridor. Imaging revealed a locally invasive necrotic mass with intense hypermetabolic activity. Histopathological examination demonstrated mixed histomorphologic features, including spindle cell, squamous, and clear cell differentiation, while subsequent molecular analysis identified BRAF V600E and TERT promoter mutations. Together, these findings supported the diagnosis of anaplastic thyroid carcinoma. Guided by a multidisciplinary tumor board, the patient underwent tracheostomy, palliative radiotherapy, and targeted therapy with dabrafenib and trametinib. However, despite initial stabilization, the patient died of progressive disease nine months after diagnosis.
This case illustrates how a decade-long latency, mixed histomorphology, and a high-risk molecular profile can complicate the recognition of anaplastic transformation. It underscores the diagnostic and therapeutic pathway required for optimal management.
G. Durham, Cindy Almaraz, C. Steinman et al.· World Journal of Biology Pha...· 0 citations
Thymic carcinoma (TC) is a rare and aggressive malignancy of the anterior mediastinum, with most patients diagnosed at advanced stages due to the absence of characteristic paraneoplastic syndromes. This review systematically synthesizes current evidence on early diagnostic modalities and immunotherapeutic strategies for TC. In diagnosis, imaging (CT, MRI), immunohistochemical markers (CD5/CD117), serum CYFRA 21-1 and circulating tumor DNA each offer distinct advantages, yet all are constrained by suboptimal sensitivity or specificity, and no single method currently enables reliable early detection. Therapeutically, immune checkpoint inhibitors (ICIs) as monotherapy yield a limited objective response rate (ORR) of approximately 18.4%, whereas ICI combined with chemotherapy, exemplified by the atezolizumab-carboplatin-paclitaxel regimen, could achieve an ORR of 56.2%, marking a substantial improvement. Notably, the incidence of grade 3-5 immune-related adverse events in TC patients (17.1%) is markedly lower than that in thymoma patients (58.3%), suggesting a more favorable safety profile for immunotherapy in TC. These findings underscore the transformative potential of chemo-immunotherapy as a first-line option for advanced TC, while also highlighting persistent challenges: the absence of validated predictive biomarkers, the limited efficacy of ICI monotherapy, and the lack of large-scale randomized controlled evidence. Future investigations should prioritize biomarker discovery, mechanistic exploration of the TC immune microenvironment, and long-term survival validation of combination regimens.
Jiaqi Cui· Theoretical and Natural Scie...· 0 citations
