This single-patient case report describes the first use of the tyrosine kinase inhibitor STI571 (imatinib) in metastatic gastrointestinal stromal tumor (GIST). The patient had chemotherapy-refractory disease driven by a c-kit exon 11 mutation. It asks whether selectively inhibiting mutant c-kit can control a tumor with no effective therapy.
This case established the core principle of targeted cancer therapy in solid tumors: if you can identify the specific molecular driver, you can inhibit it. GIST is defined by CD117 (c-kit) positivity and driven by gain-of-function c-kit mutations, most commonly in exon 11. Remember this triad for the exam: mesenchymal GI tumor, CD117-positive, c-kit mutation.
Before STI571, metastatic GIST was chemotherapy-refractory and invariably fatal, and this patient had already failed surgery, doxorubicin-based chemotherapy, thalidomide, and interferon. A single oral agent produced a 52% volume reduction and complete metabolic PET response within a month, with only grade 1 toxicity.
The practical teaching point is that FDG-PET detects response to targeted therapy far earlier than size-based imaging, which matters when deciding whether a targeted drug is working. Any suspected mesenchymal GI tumor should be worked up with CD117 staining, because the diagnosis directly determines whether imatinib therapy applies.
This single-patient case report describes the first use of the tyrosine kinase inhibitor STI571 (imatinib) in metastatic gastrointestinal stromal tumor (GIST). The patient had chemotherapy-refractory disease driven by a c-kit exon 11 mutation. It asks whether selectively inhibiting mutant c-kit can control a tumor with no effective therapy.
This case established the core principle of targeted cancer therapy in solid tumors: if you can identify the specific molecular driver, you can inhibit it. GIST is defined by CD117 (c-kit) positivity and driven by gain-of-function c-kit mutations, most commonly in exon 11. Remember this triad for the exam: mesenchymal GI tumor, CD117-positive, c-kit mutation.
Before STI571, metastatic GIST was chemotherapy-refractory and invariably fatal, and this patient had already failed surgery, doxorubicin-based chemotherapy, thalidomide, and interferon. A single oral agent produced a 52% volume reduction and complete metabolic PET response within a month, with only grade 1 toxicity.
The practical teaching point is that FDG-PET detects response to targeted therapy far earlier than size-based imaging, which matters when deciding whether a targeted drug is working. Any suspected mesenchymal GI tumor should be worked up with CD117 staining, because the diagnosis directly determines whether imatinib therapy applies.