Molecular and Clinical Approach to Intra-abdominal Adverse Effects of Targeted Cancer Therapies

Abstract

Targeted cancer therapies encompass an exponentially growing number of agents that involve a myriad of molecular pathways. To excel within this rapidly changing field of clinical oncology, radiologists must eschew traditional organ system-based approaches of cataloging adverse effects in favor of a conceptual framework that incorporates molecular mechanisms and associated clinical outcomes. Understanding molecular mechanisms that underlie imaging manifestations of adverse effects and known associations with treatment response allows radiologists to more effectively recognize adverse effects and differentiate them from tumor progression. Radiologists can therefore more effectively guide oncologists in the management of adverse effects and treatment decisions regarding continuation or cessation of drug therapy. Adverse effects from targeted cancer therapies can be classified into four categories: (a) category 1, on-target adverse effects associated with treatment response; (b) category 2, on-target adverse effects without associated treatment response; (c) category 3, off-target adverse effects; and (d) category 4, tumor necrosis-related adverse effects. This review focuses on adverse effects primarily within the abdomen and pelvis classified according to established or hypothesized molecular mechanisms and illustrated with images of classic examples and several potential emerging toxic effects. RSNA, 2017.

A rare case of intestinal lymphangiectasia induced by pazopanib

“…We believe that the clinical course of our patient indicates that pazopanib plays an important role in the development of intestinal lymphangiectasia. A review of molecularly targeted drugs showed the possible development of intestinal lymphangiectasia in patients taking pazopanib or axitinib [5]. Pazopanib is a multikinase inhibitor with VEGFR, platelet-derived growth factor receptor, and Kit as its target molecules, and these effects may have caused the development of intestinal lymphangiectasia in the present case.…”

Association between multitarget tyrosine kinase inhibitors and changes in CT appearance of submucosal fat in the gastrointestinal tract

“…SMF in patients treated with mtTKIs could possibly represent intestinal lymphangiectasia, a rare disease caused by either congenital abnormal lymphatic development or an acquired lymphatic obstruction. Lymphangiectasia in patients on antiangiogenic TKIs has been reported only once before, by Chang et al, 11 who suggested that intestinal lymphangiectasia in patients receiving VEGF TKIs may be related to VEGF's important role in lymphatic development, 20 and alterations in gene expression of VEGFR in patients with idiopathic intestinal lymphangiectasia. 21 In our study, small bowel was involved in 5/7 (71.4%) patients with positive SMF, slightly more frequent than the large bowel (3/7; 42.9%).…”

“…A literature search revealed only an annotation of this phenomenon, and no studies have previously assessed these findings and their association with TKI treatment. 11…”

“…A literature search revealed only an annotation of this phenomenon, and no studies have previously assessed these findings and their association with TKI treatment. 11 Our aim was to evaluate whether SMF is limited to patients receiving VEGFR mtTKIs, or whether this finding is more widespread and occurs in patients treated with the more selective single-target tyrosine kinase inhibitors (stTKIs). Secondary aims were to assess time of onset of SMF during treatment, SMF severity and distribution throughout the gastrointestinal tract (GIT), whether these changes were reversible after treatment cessation, and the clinical manifestations of these findings.…”

Time-dependent effect of deuterium depletion on tumor growth and metastasis

“…Targeted therapy based on suppression of specific genes or molecules contributing to malignant transformation and progression of tumor growth is a promising strategy to arrest cancer cells' division and spread. The main disadvantage of targeted therapy is ability to hit only one molecular target whereas a huge number of molecules and signaling pathways mediate malignant state of cells, and it also has serious side effects [4][5][6].…”