Possibility of molecular targeting therapy for the treatment of cancer of unknown primary origin by analysis of intracellular signaling molecules

Abstract

Recently, antibody-mediated epidermal growth factor receptor (EGFR) blockade has become a major research focus, and a number of clinical studies on this new treatment have been started in the field of clinical oncology. This retrospective study investigated the role of KRAS gene mutations and clinical features for possibilities for new therapies in patients with cancer of unknown primary (CUP). We investigated the role of KRAS, PIK3CA and BRAF gene mutations and clinical features for possibilities for new therapies in patients with CUP. Nine patients with metastases from an unknown primary tumor were included in this retrospective study. The KRAS, BRAF and PI3KCA mutational analyses were carried out by means of PCR using genomic DNA for each PCR reaction. The mutation rate in CUP for codon 12 or 13 of the KRAS gene and for PIK3CA was lower than that in colorectal cancer, while the same mutation rate for BRAF was almost the same in the two; this means that the EGFR antibodies can possibly treat CUP.

Mutation analysis concerning possibility of cancer of unknown primary new treatment

“…In agreement with previously published data, our study showed a high prevalence of BRAF mutations in melanoma (44%) and, to much lesser extent, in thyroid, colorectal, and ovarian cancer (8%, 6%, and 5%, respectively). In regard to individual aberrations, oncogenic mutations in two hot-spot regions (exons 9 and 20) of PIK3CA have been identified in various malignancies, including common tumors such as breast, lung, colorectal, ovarian and uterine (Table 3) [6,11]. In this study, PIK3CA mutations were identified in 11% of diverse tumor types.…”

“…Functional RAS may also be potentially important for regulating the actin cytoskeleton, which was suggested as being a critical driver of oncogenic transformation [19]. We analyzed the mutation of same part of these 3 genes in 9 cases of CUP in our previous reports [6] (Table 3), and mutation was detected in one case each of KRAS and BRAF. In the 2 cases analyzed in the present study, mutation was detected in 1 case of PIK3CA ( Table 3).…”

“…Exons 11 and 15 of the BRAF gene, including the classical mutation V600E, were amplified using previously described conditions and primers [6].…”

“…Certain mutations in the KRAS gene are currently the most widely used predictors for the effectiveness of EGFRinhibiting drugs in colorectal cancer. The present retrospective study investigated the role of KRAS gene mutations and other clinical features in patients with cancer of unknown primary site (CUP) [5,6]. We have analyzed additional cases with the recently improved methods for KRAS analysis and report the data of these cases.…”

Immunotherapy Combined With Chemotherapy and Radiotherapy for a Patient With Cancer of Unknown Primary: A Case Report

“…3 Ohta et al found that patients with CUP who received chemotherapy showed a relatively good prognosis. 4 However, chemotherapy has no impact on overall survival. Notably, gene detection can identify the source of CUP tissues, while another promising strategy involves liquid biopsies that detect circulating tumor DNA in patients with CUP.…”