Cancer Research and Treatment

Special Article

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; Cancer Res Treat. 2024;56(3):721-742. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.1043

Abstract PDF PubReader ePub: In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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Original Articles

Lymphoma

Forkhead Box C1 (FOXC1) Expression in Stromal Cells within the Microenvironment of T and NK Cell Lymphomas: Association with Tumor Dormancy and Activation: Ji Hae Nahm, Woo Ick Yang, Sun Och Yoon; Cancer Res Treat. 2020;52(4):1273-1282. Published online July 3, 2020; DOI: https://doi.org/10.4143/crt.2020.032

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Purpose
Forkhead box C1 (FOXC1) is critical for maintaining bone marrow microenvironments during hematopoiesis, but its role in hematological malignancies remains obscure. Here, we investigated whether FOXC1 regulates tumor dormancy and activation in the microenvironments of T and natural killer (NK) cell lymphomas.
Materials and Methods
One hundred and twenty cases of T and NK cell lymphomas were included; the immunohistochemical expression of FOXC1 was investigated in stromal cells, and numbers of FOXC1⁺ stromal cells were counted. Furthermore, the expression of phosphorylated p38 (p-p38) and phosphorylated ERK1/2 (p-ERK1/2) in tumor cells was investigated using immunohistochemistry.
Results
FOXC1 was variably expressed in C-X-C motif chemokine 12–associated reticular stromal cells, histiocytes, (myo)fibroblasts, and endothelial cells. The phenotypes of cases were categorized as dormant (high p-p38/low p-ERK1/2; n=30, 25.0%), active (high p-ERK1/2/low p-p38; n=25, 20.8%), or intermediate (others; n=65, 54.2%). Lower FOXC1⁺ stromal cell infiltration was associated with the dormant phenotype, the precursor T lymphoblastic leukemia/lymphoma subtype, and inferior overall survival rates, whereas higher FOXC1⁺ stromal cell infiltration was associated with the active phenotype and favorable patient prognosis (p < 0.05 for all).
Conclusion
These results suggested that FOXC1⁺ stromal cells within the microenvironments of T and NK cell lymphomas might be related to tumor phenotypes.

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Mechanisms of lymphoma-stromal interactions focusing on tumor-associated macrophages, fibroblastic reticular cells, and follicular dendritic cells
Rintaro Ohe
Journal of Clinical and Experimental Hematopathology.2024; 64(3): 166. CrossRef

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Investigating Trk Protein Expression between Oropharyngeal and Non-oropharyngeal Squamous Cell Carcinoma: Clinical Implications and Possible Roles of Human Papillomavirus Infection: Yoon Ah Cho, Ji Myung Chung, Hyunmi Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon; Cancer Res Treat. 2019;51(3):1052-1063. Published online October 24, 2018; DOI: https://doi.org/10.4143/crt.2018.411

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Purpose
The relationship between head and neck squamous cell carcinoma (HNSCC) and subtypes of tropomyosin-related kinase (Trk) has not been studied in-depth. In this study, we evaluated the expression patterns of TrkA, TrkB, and panTrk and their clinicopathological significance as well as association with p16 expression and human papilloma virus (HPV) status.
Materials and Methods
Total of 396 radically resected oropharyngeal (n=121) and non-oropharyngeal (n=275) HNSCCs were included. Immunohistochemistry for TrkA, TrkB, and panTrk was performed. In addition, p16 immunohistochemistry was performed to assess the HPV status. Using HPV-negative HNSCC cell lines, FaDu and CAL27, HPV type 16 E6/E7 gene was transfected, and then changes of TrkA and TrkB expression were analyzed.
Results
In the clinical samples of HNSCC, high expression of TrkA and panTrk were more associated with oropharyngeal and p16 positive squamous cell carcinoma (SCC). In patients with completely resected (R0-resected) oropharyngeal SCC, high TrkA expression was related to superior overall survival and recurrence-free survival (RFS). In patients with R0-resected oral cavity SCC, high panTrk was related to poor RFS. In HPV type E6/E7 gene-transfected FaDu and CAL27 cell lines, increase of TrkA expression was observed.
Conclusion
It seems that expression pattern of panTrk and TrkA differed according to anatomical sites of HNSCC and was closely related to p16 expression and patient prognosis. Trk expression should be considered in the context of anatomical site, p16 expression or HPV status and Trk subtypes.

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NTRK Gene Expression Analysis in Oral Squamous Cell Carcinoma Mexican Population
Lilibeth Stephania Escoto-Vasquez, Javier Portilla-Robertson, Josué Orlando Ramírez-Jarquín, Luis Fernando Jacinto-Alemán, Alejandro Alonso-Moctezuma, Carla Monserrat Ramírez-Martínez, Osmar Alejandro Chanes-Cuevas, Fabiola Salgado-Chavarria
Dentistry Journal.2024; 12(10): 327. CrossRef
Accuracy of magnetic resonance imaging in the assessment of depth of invasion in tongue carcinoma: A systematic review and meta-analysis
Kondajji Ramachandra Vijayalakshmi, Vanshika Jain
National Journal of Maxillofacial Surgery.2023; 14(3): 341. CrossRef
CYLD Alterations in the Tumorigenesis and Progression of Human Papillomavirus–Associated Head and Neck Cancers
Zhibin Cui, Hyunseok Kang, Jennifer R. Grandis, Daniel E. Johnson
Molecular Cancer Research.2021; 19(1): 14. CrossRef
Genome-wide analysis identifies critical DNA methylations within NTRKs genes in colorectal cancer
Zijian Chen, Zenghong Huang, Yanxin Luo, Qi Zou, Liangliang Bai, Guannan Tang, Xiaolin Wang, Guangwen Cao, Meijin Huang, Jun Xiang, Huichuan Yu
Journal of Translational Medicine.2021;[Epub] CrossRef
Ferroportin and FBXL5 as Prognostic Markers in Advanced Stage Clear Cell Renal Cell Carcinoma
Cheol Keun Park, Jayoon Heo, Won Sik Ham, Young-Deuk Choi, Sang Joon Shin, Nam Hoon Cho
Cancer Research and Treatment.2021; 53(4): 1174. CrossRef
Clinical Significance of Trk Receptor Expression as a New Therapeutic Target in Hepatocellular Carcinoma
Sangjoon Choi, Sujin Park, Yoon Ah Cho, Cheol-Keun Park, Sang Yun Ha
Pathology & Oncology Research.2020; 26(4): 2587. CrossRef
Overexpression of wild type or a Q311E mutant MB21D2 promotes a pro‐oncogenic phenotype in HNSCC
Daniel E. Gracilla, Praveen Kumar Korla, Ming‐Tsung Lai, An‐Jen Chiang, Wen‐Shiung Liou, Jim Jinn‐Chyuan Sheu
Molecular Oncology.2020; 14(12): 3065. CrossRef
NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma
Eun Kyung Kim, Yoon Ah Cho, Mi-kyoung Seo, Hyunmi Ryu, Byoung Chul Cho, Yoon Woo Koh, Sun Och Yoon
Scientific Reports.2019;[Epub] CrossRef
Characterization of head and neck squamous cell carcinoma arising in young patients: Particular focus on molecular alteration and tumor immunity
Hyang Joo Ryu, Eun Kyung Kim, Byoung Chul Cho, Sun Och Yoon
Head & Neck.2019; 41(1): 198. CrossRef

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Overexpression of Endoplasmic Reticulum Oxidoreductin 1-α (ERO1L) Is Associated with Poor Prognosis of Gastric Cancer: So-Young Seol, Chul Kim, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho; Cancer Res Treat. 2016;48(4):1196-1209. Published online February 26, 2016; DOI: https://doi.org/10.4143/crt.2015.189

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Purpose
Gastric cancer is the second leading cause of cancer-related death worldwide. Although surgery is the standard curative treatment for gastric cancer, relapse occurs in a large number of patients, except in the case of early diagnosed gastric cancer. Following previous studies that identified endoplasmic reticulum oxidoreductin 1-α (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer.
Materials and Methods
For validation of microarray data, the mRNA expression level of ERO1L was measured by quantitative real-time reverse transcription polymerase chain reaction in 56 independent stage III gastric cancer patients. Immunohistochemical staining was performed to examine the protein expression level of ERO1L in 231 gastric cancer patients. Correlation between gene expression and cancer prognosis was evaluated.
Results
Patients with high ERO1L expression had poorer survival than those with low expression (p < 0.01). Functional assays demonstrated that ERO1L knockdown inhibited cell proliferation, migration, invasion, and chemoresistance. In addition, involvement of inactivation of Akt and JNK signaling in molecular mechanisms of ERO1L inhibition was demonstrated.
Conclusion
High expression of ERO1L is associated with poor prognosis of patients with gastric cancer. These results indicate that ERO1L expression may be a clinically promising therapeutic target for prevention of gastric cancer.

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Biological mechanisms and clinical significance of endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) in human cancer
Peng Chen, Amit Sharma, Hans Weiher, Ingo G.H. Schmidt-Wolf
Journal of Experimental & Clinical Cancer Research.2024;[Epub] CrossRef
Cordycepin reprogramming lipid metabolism to block metastasis and EMT via ERO1A/mTOR/SREBP1 axis in cholangiocarcinoma
Xuebing Zhou, Yuan Li, Chunyu Yang, Dan Chen, Tong Wang, Tesi Liu, Wendi Yan, Zhaoxia Su, Bosen Peng, Xiangshan Ren
Life Sciences.2023; 327: 121698. CrossRef
ERO1α promotes the proliferation and inhibits apoptosis of colorectal cancer cells by regulating the PI3K/AKT pathway
Min Wu, Ruixue Li, Jianyan Qin, Ziyuan Wang, Jiasen Guo, Fenghong Lv, Guoqin Wang, Youguang Huang
Journal of Molecular Histology.2023; 54(6): 621. CrossRef
Identification of novel small molecule inhibitors for endoplasmic reticulum oxidoreductase 1α (ERO1α) enzyme: structure-based molecular docking and molecular dynamic simulation studies
Hussam Albassam, Chetan H. Mehta, Usha Y. Nayak
Journal of Biomolecular Structure and Dynamics.2022; 40(23): 13218. CrossRef
MicroRNA-218-5p affects lung adenocarcinoma progression through targeting endoplasmic reticulum oxidoreductase 1 alpha
Gang Chen, Qihao Wang, Kunyu Wang
Bioengineered.2022; 13(4): 10061. CrossRef
ERO1L promotes the proliferation and metastasis of lung adenocarcinoma via the Wnt2/β‐catenin signaling pathway
Jinbao Xie, Guoliang Liao, Zhi Feng, Bo Liu, Xu Li, Minglian Qiu
Molecular Carcinogenesis.2022; 61(10): 897. CrossRef
Current therapeutic options for gastric adenocarcinoma
C.R. Akshatha, Smitha Bhat, R. Sindhu, Dharini Shashank, Sarana Rose Sommano, Wanaporn Tapingkae, Ratchadawan Cheewangkoon, Shashanka K. Prasad
Saudi Journal of Biological Sciences.2021; 28(9): 5371. CrossRef
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Dandan Huang, Cuimei Li
Oncology Letters.2021;[Epub] CrossRef
Increased Progastrin-Releasing Peptide Expression is Associated with Progression in Gastric Cancer Patients
Li Li, Xiaodong Yin, Hai Meng, Juanyu Hu, Zhengqing Yu, Jianyong Xu
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Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities
Zifeng Song, Martin C. Pearce, Yuan Jiang, Liping Yang, Cheri Goodall, Cristobal L. Miranda, Milan Milovancev, Shay Bracha, Siva K. Kolluri, Claudia S. Maier
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Role of the ERO1-PDI interaction in oxidative protein folding and disease
Andrea G. Shergalis, Shuai Hu, Armand Bankhead, Nouri Neamati
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Perineural Invasion and Postoperative Adjuvant Chemotherapy Efficacy in Patients With Gastric Cancer
Qing Tao, Wen Zhu, Xiaohui Zhao, Mei Li, Yongqian Shu, Deqiang Wang, Xiaoqin Li
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ERO1L promotes NSCLC development by modulating cell cycle‐related molecules
Xiujuan Shi, Jiawen Wu, Yi Liu, Yuxiong Jiang, Changjiang Zhi, Jue Li
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ERO1L promotes IL6/sIL6R signaling and regulates MUC16 expression to promote CA125 secretion and the metastasis of lung cancer cells
Yuanyuan lei, Ruochuan Zang, Zhiliang Lu, Guochao Zhang, Jianbing Huang, Chengming Liu, Zhanyu Wang, Shuangshuang Mao, Yun Che, Xinfeng Wang, Sufei Zheng, Lingling Fang, Nan Sun, Jie He
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ROS Generation and Antioxidant Defense Systems in Normal and Malignant Cells
Anastasiya V. Snezhkina, Anna V. Kudryavtseva, Olga L. Kardymon, Maria V. Savvateeva, Nataliya V. Melnikova, George S. Krasnov, Alexey A. Dmitriev
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Daria Sicari, Aeid Igbaria, Eric Chevet
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ERO1α promotes hypoxic tumor progression and is associated with poor prognosis in pancreatic cancer
Nikhil Gupta, Jung Eun Park, Wilford Tse, Jee Keem Low, Oi Lian Kon, Neil McCarthy, Siu Kwan Sze
Oncotarget.2019; 10(57): 5970. CrossRef
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Prognostic Significance of Defining L-Cell Type on the Biologic Behavior of Rectal Neuroendocrine Tumors in Relation with Pathological Parameters: The Gastrointestinal Pathology Study Group of Korean Society of Pathologists, Jin Hee Sohn, Mee-Yon Cho, Yangsoon Park, Hyunki Kim, Woo Ho Kim, Joon Mee Kim, Eun Sun Jung, Kyoung-Mee Kim, Jae Hyuk Lee, Hee Kyung Chan, Do Youn Park, Mee Joo, Sujin Kim, Woo Sung Moon, Mi Seon Kang, So-Young Jin, Yun Kyung Kang, Sun Och Yoon, HyeSeung Han, EunHee Choi; Cancer Res Treat. 2015;47(4):813-822. Published online February 26, 2015; DOI: https://doi.org/10.4143/crt.2014.238

Abstract PDF PubReader ePub

Purpose
In 2010, the World Health Organization categorized L-cell type neuroendocrine tumors (NETs) as tumors of uncertain malignancy, while all others were classified as malignant. However, the diagnostic necessity of L-cell immunophenotyping is unclear, as are tumor stage and grade that may guide diagnosis and management. To clarify the predictive markers of rectal neuroendocrine neoplasms (NENs), 5- and 10-year overall survival (OS) was analyzed by pathological parameters including L-cell phenotype. Materials and Methods A total of 2,385 rectal NENs were analyzed from our previous multicenter study and a subset of 170 rectal NENs was immunophenotyped.
Results
In univariate survival analysis, tumor grade (p < 0.0001), extent (p < 0.0001), size (p < 0.0001), lymph node metastasis (p=0.0063), and L-cell phenotype (p < 0.0001) showed significant correlation with the prognosis of rectal NENs; however, none of these markers achieved independent significance in multivariate analysis. The 10-year OS of tumors of NET grade 1, < 10 mm, the mucosa/submucosa was 97.58%, 99.47%, and 99.03%, respectively. L-Cell marker, glucagon II (GLP-1&2), with a cut off score of > 10, is useful in defining L-Cell type. In this study, an L-cell immunophenotype was found in 83.5% of all rectal NENs and most, but not all L-cell type tumors were NET G1, small (< 10 mm) and confined to the mucosa/submucosa. Conclusion From these results, the biological behavior of rectal NENs does not appear to be determined by L-cell type alone but instead by a combination of pathological parameters.

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Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors
Joo Young Kim, Jisup Kim, Yong-il Kim, Dong-Hoon Yang, Changhoon Yoo, In Ja Park, Baek-Yeol Ryoo, Jin-Sook Ryu, Seung-Mo Hong
Scientific Reports.2024;[Epub] CrossRef
The Clinicopathological Significance of Tumor Cell Subtyping in Appendiceal Neuroendocrine Tumors: A Series of 135 Tumors
Ozgur Mete, David W. Dodington, Daniel L. Shen, Sylvia L. Asa
Endocrine Pathology.2024; 35(2): 107. CrossRef
Cauda Equina Neuroendocrine Tumors
Sylvia L. Asa, Ozgur Mete, Ulrich Schüller, Biswarathan Ramani, Kanish Mirchia, Arie Perry
American Journal of Surgical Pathology.2023; 47(4): 469. CrossRef
Diagnostic, Prognostic, and Predictive Role of Ki67 Proliferative Index in Neuroendocrine and Endocrine Neoplasms: Past, Present, and Future
Stefano La Rosa
Endocrine Pathology.2023; 34(1): 79. CrossRef
Clinicopathologic Impact of Peptide Hormonal Expression in Rectal Neuroendocrine Tumors
Jisup Kim, Dong-Hoon Yang, HaeSung Jung, HyungJun Cho, Hyeung-Jin Jang, Changhoon Yoo, In Ja Park, Baek-Yeol Ryoo, Jin-Sook Ryu, Seung-Mo Hong
Archives of Pathology & Laboratory Medicine.2023; 147(7): 797. CrossRef
Rectal Neuroendocrine Neoplasms: Why Is There a Global Variation?
Jack Cope, Raj Srirajaskanthan
Current Oncology Reports.2022; 24(3): 257. CrossRef
Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms
Guido Rindi, Ozgur Mete, Silvia Uccella, Olca Basturk, Stefano La Rosa, Lodewijk A. A. Brosens, Shereen Ezzat, Wouter W. de Herder, David S. Klimstra, Mauro Papotti, Sylvia L. Asa
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Kai Duan, Ozgur Mete
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Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study: Mee-Yon Cho, Joon Mee Kim, Jin Hee Sohn, Mi-Jung Kim, Kyoung-Mee Kim, Woo Ho Kim, Hyunki Kim, Myeong-Cherl Kook, Do Youn Park, Jae Hyuk Lee, HeeKyung Chang, Eun Sun Jung, Hee Kyung Kim, So-Young Jin, Joon Hyuk Choi, Mi Jin Gu, Sujin Kim, Mi Seon Kang, Chang Ho Cho, Moon-Il Park, Yun Kyung Kang, Youn Wha Kim, Sun Och Yoon, Han Ik Bae, Mee Joo, Woo Sung Moon, Dae Young Kang, Sei Jin Chang; Cancer Res Treat. 2012;44(3):157-165. Published online September 30, 2012; DOI: https://doi.org/10.4143/crt.2012.44.3.157

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PURPOSE
As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea.
MATERIALS AND METHODS
We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters.
RESULTS
Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET.
CONCLUSION
The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

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Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors
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Prognostic Factors of Second and Third Line Chemotherapy Using 5-FU with Platinum, Irinotecan, and Taxane for Advanced Gastric Cancer: Ji Soo Park, Jae Yun Lim, Seung Kyo Park, Min Kyung Kim, Hee Sung Ko, Sun Och Yoon, Jong Won Kim, Seung Ho Choi, Jae Yong Cho; Cancer Res Treat. 2011;43(4):236-243. Published online December 27, 2011; DOI: https://doi.org/10.4143/crt.2011.43.4.236

Abstract PDF PubReader ePub

PURPOSE
The aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third-line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response.
MATERIALS AND METHODS
Fifty gastric carcinoma patients who were treated by third-line sequential chemotherapy between November 2004 and July 2010 were enrolled in this study. Their overall survival (OS) and time to progression (TTP) were set up as primary and secondary end points. For the sequence of chemotherapy regimen, two arms were used. Arm A was defined as 5-fluorouracil (5-FU)+cisplatin (FP) or folinic acid, 5-FU and oxaliplati (FOLFOX), followed by folinic acid, 5-FU and irinotecan (FOLFIRI), and paclitaxel or docetaxel plus 5-FU, with or without epirubicin. Arm B was defined as FP or FOLFOX, followed by paclitaxel or docetaxel plus 5-FU, and FOLFIRI.
RESULTS
The median OS of all patients was 16.0 months (95% confidence interval, 13.6 to 18.3 months), which is longer than historical control of patients who did not receive third-line chemotherapy. The sequence of second and third-line regimen, including irinotecan and taxane, did not present significant difference in OS or TTP after failure of 5-FU with platinum chemotherapy. In survival analysis of patients' clinicopathologic characteristics, poor prognosis was shown in patients with poorly differentiated histologic features, elevated serum carcinoembryonic level, and shorter TTP of first line chemotherapy.
CONCLUSION
It is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles. Development of individualized chemotherapy regimens based on gene expression profiles is warranted.

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