RARE DISEASE
Inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor
Drug discovery
1
drug
With orphan designation
Overview
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate malignant potential, characterized by myofibroblastic spindle cells, chronic inflammatory infiltrates, and frequent ALK gene rearrangements (50-80% of cases). It primarily affects young individuals, with local recurrence rates up to 30% and rare metastasis. Definitive diagnosis requires histopathology (spindle cells + inflammation) and molecular testing for ALK/ROS1/NTRK fusions.
Therapies
Localized disease: Complete surgical resection (curative in 70-80% of cases) [3][16][18].
Advanced/unresectable: ALK inhibitors (crizotinib, alectinib) for ALK-positive tumors (≥50% response), chemotherapy (anthracycline or methotrexate-based regimens), or radiotherapy [2][8][18].
Emerging options: Targeted therapy for ROS1/NTRK/RET fusions and immunotherapy trials [8][13].
Categories: rare neoplastic diseases
Research Papers
672 drug discovery papers about Inflammatory myofibroblastic tumor, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
672 drug discovery papers about Inflammatory myofibroblastic tumor, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-13 | Gastric inflammatory myofibroblastic tumor in adults: a case report and literature review.
Gastric inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, with adult cases being particularly uncommon. We report a 64-year-old man with an incidentally detected gastric mass that was preoperatively suspected to be a gastrointestinal stromal tumor (GIST). The relevant literature on adult gastric IMT was also reviewed. Complete surgical resection with negative margins (R0 resection) remains the mainstay of treatment, whereas patients with confirmed ALK rearrangements may benefit from ALK inhibitor therapy. Histopathological confirmation and long-term surveillance are essential because of the potential for recurrence and occasional aggressive behavior.
2026-08-11 | Case Report: Dose-escalated volumetric modulated arc therapy achieving bowel and renal protection for large retroperitoneal inflammatory myofibroblastic tumor invading ureter and inferior vena cava
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm for which definitive radiotherapy in the retroperitoneum remains largely undefined, particularly when dose escalation must be balanced against the preservation of adjacent critical organs. A 59-year-old woman presented with a 10-day history of fever and abdominopelvic pain. Physical examination revealed deep tenderness in the right lower quadrant, and laboratory testing demonstrated leukocytosis. Imaging identified a 9.2 cm retroperitoneal mass invading the right ureter and inferior vena cava. Biopsy confirmed IMT, and capture-based next-generation sequencing revealed no class I actionable alterations. Given the unfavorable surgical anatomy and limited response to corticosteroids, curative-intent resection was precluded. The patient was treated with definitive dose-escalated volumetric modulated arc therapy (VMAT) employing a simultaneous integrated boost strategy (66 Gy/33 fractions to the boost volume and 50 Gy to the conventional planning target volume), with spatial sparing of adjacent organs at risk. Complete radiographic response was achieved at one month, without grade ≥2 treatment-related adverse events. At 19-month follow-up, the patient remained disease-free with stable renal function. This case demonstrates that dose-escalated VMAT with spatial organ avoidance can achieve durable complete remission in unresectable retroperitoneal IMT while preserving organ function, supporting its consideration as a curative-intent strategy in this challenging clinical setting.
2026-08-05 | Inflammatory myofibroblastic tumour: unravelling the interplay of inflammation, kinase signalling, and therapeutic resistance.
Inflammatory myofibroblastic tumour (IMT) is a mesenchymal tumour characterised by myofibroblastic cells and the presence of inflammatory cells, such as macrophages, neutrophils, and lymphocytes. IMT can originate from diverse anatomical locations within the body. The macrophage-rich immune microenvironment contributes to cytokine release and inflammation, but IMT is primarily driven by oncogenic alterations. Oncogenic fusions, most commonly involving anaplastic lymphoma kinase (ALK), and other genes, such as ROS1 and NTRK3, are seen in most IMTs. Upregulation of these genes activates downstream signalling pathways such as RAS/MAPK and PI3K/AKT, leading to uncontrolled cell proliferation. Constitutive tyrosine kinase activation disrupts cell-cycle control by suppressing p21/p27, inactivating Rb, and impairing p53-dependent checkpoints, thereby limiting apoptosis. Combining surgery with targeted kinase inhibitors remains the primary therapeutic approach, especially for ALK-positive IMT. On the contrary, ALK-negative IMT harbours distinct oncogenic fusions and is driven by diverse signalling pathways. Thus, it requires therapeutic methods targeting the specific molecular alterations. Resistance to ALK inhibitors can emerge during treatment. This resistance arises through bypass signalling, epigenetic changes, and secondary mutations. This review aims to analyse the interplay between inflammation and genetic fusions in the origin and progression of IMT. The review provides an overview of the therapeutic approaches currently in use, mechanisms of treatment resistance, and potential techniques to improve diagnosis and develop personalised therapeutic strategies.
2026-07-29 | Precision oncology for ALK positive inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with a broad clinical spectrum, ranging from indolent localized lesions to aggressive metastatic disease. Approximately half of IMTs harbor oncogenic anaplastic lymphoma kinase (ALK) gene fusions, which drive constitutive kinase activation and render the tumors sensitive to ALK tyrosine kinase inhibitors (ALK-TKIs). Although ALK-targeted therapy has significantly improved outcomes in IMT patients, durable responses are frequently limited by intrinsic and acquired resistance. In this review, we summarize the molecular taxonomy and functional stratification of ALK fusion variants in IMT, highlighting their diagnostic and therapeutic implications. We outline a tiered diagnostic workflow integrating immunohistochemistry, fluorescence in situ hybridization, and RNA-based next-generation sequencing to optimize fusion detection and guide precision treatment selection. We also discuss the major mechanisms of ALK-TKIs resistance—including on-target kinase domain mutations, off-target bypass pathway activation, and lineage plasticity—and propose corresponding clinical countermeasures. Finally, we review emerging therapeutic strategies such as third-generation ALK-TKIs, TRK-sparing brain-penetrant compounds, PROTAC-based degraders, combination regimens, and ctDNA-guided monitoring, aiming to support precision oncology decision-making and improve long-term outcomes for patients with ALK-positive IMT.
2026-07-22 | Endobronchial mass in an adult: an unusual presentation of inflammatory myofibroblastic tumour.
Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, most commonly affecting children and young adults, with the lung being one of the the most common sites. Its variable clinical, radiological and pathological features often mimic malignancy, making diagnosis challenging. We report a middle-aged man in his early 50s presenting with life-threatening haemoptysis and found to have a right main bronchus mass causing central airway obstruction. Emergency rigid bronchoscopy with cryo-debulking was performed for airway stabilisation and tissue diagnosis. Histopathology confirmed IMT. Immunohistochemistry was anaplastic lymphoma kinase negative, while molecular analysis demonstrated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) positivity, highlighting the molecular heterogeneity of IMT. Following multidisciplinary tumour board discussion, the patient was initiated on targeted therapy with crizotinib, with planned reassessment for surgical resection. This case emphasises the importance of early tissue diagnosis, molecular profiling and multidisciplinary decision-making in achieving personalised and potentially lung-sparing treatment.
2026-08-13 | Gastric inflammatory myofibroblastic tumor in adults: a case report and literature review.
Gastric inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, with adult cases being particularly uncommon. We report a 64-year-old man with an incidentally detected gastric mass that was preoperatively suspected to be a gastrointestinal stromal tumor (GIST). The relevant literature on adult gastric IMT was also reviewed. Complete surgical resection with negative margins (R0 resection) remains the mainstay of treatment, whereas patients with confirmed ALK rearrangements may benefit from ALK inhibitor therapy. Histopathological confirmation and long-term surveillance are essential because of the potential for recurrence and occasional aggressive behavior.
2026-08-11 | Case Report: Dose-escalated volumetric modulated arc therapy achieving bowel and renal protection for large retroperitoneal inflammatory myofibroblastic tumor invading ureter and inferior vena cava
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm for which definitive radiotherapy in the retroperitoneum remains largely undefined, particularly when dose escalation must be balanced against the preservation of adjacent critical organs. A 59-year-old woman presented with a 10-day history of fever and abdominopelvic pain. Physical examination revealed deep tenderness in the right lower quadrant, and laboratory testing demonstrated leukocytosis. Imaging identified a 9.2 cm retroperitoneal mass invading the right ureter and inferior vena cava. Biopsy confirmed IMT, and capture-based next-generation sequencing revealed no class I actionable alterations. Given the unfavorable surgical anatomy and limited response to corticosteroids, curative-intent resection was precluded. The patient was treated with definitive dose-escalated volumetric modulated arc therapy (VMAT) employing a simultaneous integrated boost strategy (66 Gy/33 fractions to the boost volume and 50 Gy to the conventional planning target volume), with spatial sparing of adjacent organs at risk. Complete radiographic response was achieved at one month, without grade ≥2 treatment-related adverse events. At 19-month follow-up, the patient remained disease-free with stable renal function. This case demonstrates that dose-escalated VMAT with spatial organ avoidance can achieve durable complete remission in unresectable retroperitoneal IMT while preserving organ function, supporting its consideration as a curative-intent strategy in this challenging clinical setting.
2026-08-05 | Inflammatory myofibroblastic tumour: unravelling the interplay of inflammation, kinase signalling, and therapeutic resistance.
Inflammatory myofibroblastic tumour (IMT) is a mesenchymal tumour characterised by myofibroblastic cells and the presence of inflammatory cells, such as macrophages, neutrophils, and lymphocytes. IMT can originate from diverse anatomical locations within the body. The macrophage-rich immune microenvironment contributes to cytokine release and inflammation, but IMT is primarily driven by oncogenic alterations. Oncogenic fusions, most commonly involving anaplastic lymphoma kinase (ALK), and other genes, such as ROS1 and NTRK3, are seen in most IMTs. Upregulation of these genes activates downstream signalling pathways such as RAS/MAPK and PI3K/AKT, leading to uncontrolled cell proliferation. Constitutive tyrosine kinase activation disrupts cell-cycle control by suppressing p21/p27, inactivating Rb, and impairing p53-dependent checkpoints, thereby limiting apoptosis. Combining surgery with targeted kinase inhibitors remains the primary therapeutic approach, especially for ALK-positive IMT. On the contrary, ALK-negative IMT harbours distinct oncogenic fusions and is driven by diverse signalling pathways. Thus, it requires therapeutic methods targeting the specific molecular alterations. Resistance to ALK inhibitors can emerge during treatment. This resistance arises through bypass signalling, epigenetic changes, and secondary mutations. This review aims to analyse the interplay between inflammation and genetic fusions in the origin and progression of IMT. The review provides an overview of the therapeutic approaches currently in use, mechanisms of treatment resistance, and potential techniques to improve diagnosis and develop personalised therapeutic strategies.
2026-07-29 | Precision oncology for ALK positive inflammatory myofibroblastic tumor
Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm with a broad clinical spectrum, ranging from indolent localized lesions to aggressive metastatic disease. Approximately half of IMTs harbor oncogenic anaplastic lymphoma kinase (ALK) gene fusions, which drive constitutive kinase activation and render the tumors sensitive to ALK tyrosine kinase inhibitors (ALK-TKIs). Although ALK-targeted therapy has significantly improved outcomes in IMT patients, durable responses are frequently limited by intrinsic and acquired resistance. In this review, we summarize the molecular taxonomy and functional stratification of ALK fusion variants in IMT, highlighting their diagnostic and therapeutic implications. We outline a tiered diagnostic workflow integrating immunohistochemistry, fluorescence in situ hybridization, and RNA-based next-generation sequencing to optimize fusion detection and guide precision treatment selection. We also discuss the major mechanisms of ALK-TKIs resistance—including on-target kinase domain mutations, off-target bypass pathway activation, and lineage plasticity—and propose corresponding clinical countermeasures. Finally, we review emerging therapeutic strategies such as third-generation ALK-TKIs, TRK-sparing brain-penetrant compounds, PROTAC-based degraders, combination regimens, and ctDNA-guided monitoring, aiming to support precision oncology decision-making and improve long-term outcomes for patients with ALK-positive IMT.
2026-07-22 | Endobronchial mass in an adult: an unusual presentation of inflammatory myofibroblastic tumour.
Inflammatory myofibroblastic tumour (IMT) is a rare mesenchymal neoplasm of intermediate biological potential, most commonly affecting children and young adults, with the lung being one of the the most common sites. Its variable clinical, radiological and pathological features often mimic malignancy, making diagnosis challenging. We report a middle-aged man in his early 50s presenting with life-threatening haemoptysis and found to have a right main bronchus mass causing central airway obstruction. Emergency rigid bronchoscopy with cryo-debulking was performed for airway stabilisation and tissue diagnosis. Histopathology confirmed IMT. Immunohistochemistry was anaplastic lymphoma kinase negative, while molecular analysis demonstrated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) positivity, highlighting the molecular heterogeneity of IMT. Following multidisciplinary tumour board discussion, the patient was initiated on targeted therapy with crizotinib, with planned reassessment for surgical resection. This case emphasises the importance of early tissue diagnosis, molecular profiling and multidisciplinary decision-making in achieving personalised and potentially lung-sparing treatment.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Inflammatory myofibroblastic tumor, including 1 approved therapy.
1 orphan drug designation for Inflammatory myofibroblastic tumor, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
crizotinib [Xalkori] | small molecules | FDA | 2021-12-20 | 2022-07-14 | Pfizer Inc. |
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