Gastrointestinal stromal cell tumors

Sunitinib (7),10 developed by Sugene/Pfizer, was approved in 2006 for the treatment of renal cell carcinoma (RCC). It is a VEGFR kinase inhibitor that slows down the angiogenesis of tumor endothelial cells, which provide nutrients and help tumor growth and metastasis. Sunitinib also blocks KIT, an oncogenic kinase that causes gastrointestinal stromal cell tumors. It was approved as a second-line anti-GSIT therapy for imatinib-resistant patients. 

Gastric adenocarcinoma is one of the leading causes of cancer morbidity and mortality worldwide. Gastric cancer comprises approximately 95% of all gastric tumors, and is the focus of this chapter. Other less common gastric tumors not discussed here include mucosa-associated lymphoid tissue (MALT) lymphoma, gastrointestinal stromal cell tumors, and carcinoid tumors. 

NHL, non-Hodgkin s lymphoma AEG, adenocarcinoma of the esophagogastreal junction SCC, squamous cell carcinoma GIST, gastrointestinal stromal tumor. 

In summary, sunitinib maleate (1) is a multitargeted receptor tyrosine kinase inhibitor with potent anti-angiogenic and antitumor activity. It is approved for the treatment of advanced renal cell carcinoma and gastrointestinal stromal tumors, and is currently undergoing clinical trials for a number of additional malignancies. The discovery synthesis of 1 along with its process development approaches were described in this chapter. 

Goodman VL, Rock EP, Dagher R, et al. Approval summary Sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma. Clin Cancer Res. 2007 13(5) 1367-1373. 

Indications Gastrointestinal stromal tumor, Metastatic renal cell carcinoma... 

ANLL, acute nonlymphocytic leukemia APE, acute promyelocytic leukemia CEL, chronic lymphocytic leukemia CML, chronic myelogenous leukemia EGER, epidermal growth factor receptor CIST, gastrointestinal stromal tumor MoAB, monoclonal antibody NE-kB, nuclear factor-KB Ph+ ALL, Philadelphia chromosome-positive acute lymphocytic leukemia PCP, Pneumocystis carinii pneumonia WBC, white blood cell. 

Gastrointestinal stromal tumor Adults. Cl tract. Abdominopelvic region. Metastases often to the liver. Spindle or epithelioid cells CD11 7-e, CD34-E, often negative for SI 00, actin, and desmin KIT activating mutations... 

Although the previously mentioned markers are helpful in distinguishing between different germ cell tumors, they are not entirely specific. CD 117 or c-kit is a marker of interstitial cell of Cajal (and therefore stains gastrointestinal stromal tumors), mast cells, and melanocytes in addition to germ cells.CD30 (+ in embryonal carcinoma) is an activation marker, often seen in... 

Sircar K, Hewlett BR, Huizinga JD, et al. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol. 1999 23 377-389. 

Yamaguchi U, Hasegawa T, Masuda T, et al. Differential diagnosis of gastrointestinal stromal tumor and other spindle cell tumors in the gastrointestinal tract based on immunohistochemical analysis. Virchows Arch. 2004 445 142-150. 

Suster S, Fletcher CD. Gastrointestinal stromal tumors with prominent signet-ring cell features. Mod Pathol. 1996 9 609-613. 

Although only one primary uterine gastrointestinal stromal tumor (GIST) has been reported, rectal examples may occasionally be mistaken for fibroids. Spindle cell examples would then suggest leiomyoma or perhaps even leiomyosarcoma, and epithelioid varieties could mimic an epithelioid smooth muscle tumor, carcinoma. 

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