Cancer Research and Treatment

Review Article

The Era of Antibody Drug Conjugates in Lung Cancer: Trick or Threat?: Mariona Riudavets, David Planchard; Cancer Res Treat. 2025;57(2):293-311. Published online November 28, 2024; DOI: https://doi.org/10.4143/crt.2024.714

Abstract PDF PubReader ePub: Antibody drug conjugates (ADCs) are a novel class of therapeutics that structurally are composed by an antibody directed to a tumor epitope connected via a linker to a cytotoxic payload, and that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology and design of ADCs, as well as we describe the results of different studies evaluating ADCs in lung cancer directed to several targets including HER2, HER3, TROP2, MET, CEACAM5 and DLL3.

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Original Articles

Predictive Value of Preoperative Serum CEA, CA19-9 and CA125 Levels for Peritoneal Metastasis in Patients with Gastric Carcinoma: Gun Ick Hwang, Chang Hak Yoo, Byung Ho Sohn, Jun Ho Shin, Yong Lai Park, Heung Dai Kim, Yong Shin Kim, Won Kon Han, Won Kil Pae; Cancer Res Treat. 2004;36(3):178-181. Published online June 30, 2004; DOI: https://doi.org/10.4143/crt.2004.36.3.178

Abstract PDF PubReader ePub

Purpose

Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. This study analyzed the usefulness of diagnostic imaging and various tumor markers in the detection of peritoneal metastasis in gastric cancer.

Materials and Methods

The sera from 768 patients with gastric cancer were measured for CEA, CA19-9 and CA125 levels using a commercial immunoradiometric assay. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound (US) before laparotomy.

Results

Preoperative levels of CEA, CA19-9 and CA125 were above the cut-off levels in 15.4%, 8.7% and 5.7% of all cases, respectively. Eighty-eight patients were diagnosed with peritoneal metastasis by laparotomy. CT and US revealed peritoneal dissemination in 15 of 88 patients (17%). Among the three tumor markers, CA19-9 and CA125 showed similar detection rates of peritoneal metastasis (37.5% and 38.6%, respectively). In particular, the serum CA125 levels showed the best sensitivity (38.6%), specificity (98.4%), and diagnostic accuracy (91.5%), and the highest odd ratio (24.46, 95% CI: 11.17~53.57) for predicting peritoneal metastasis among the markers tested. CEA did not add significant predictive information (p=0.471).

Conclusion

Preoperative serum CA19-9 and CA125 levels may provide a predictable value in determining peritoneal metastasis in patients with gastric cancer.

Citations

Citations to this article as recorded by

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Clinical Significance of Peripheral Blood CEA mRNA Expression in Gastric Cancer Patients Underwent Curative Resection: Jae Hong Seo, Sun Hee Park, Chang Won Bak, Chul Won Choi, Byoung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim, Young Jae Mok, Jong Suk Kim, Seon Ae Han, Jung In Yoon; Cancer Res Treat. 2001;33(6):483-488. Published online December 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.6.483

Abstract PDF: PURPOSE
Recent advances in molecular technology have made it possible to detect small numbers of circulating tumor cells in the peripheral blood or bone marrow. Carcinoembryonic antigen (CEA) is an oncofetal antigen that is expressed in epithelial tumor cells. CEA mRNA may be a reliable marker for the detection of tumor cells in the peripheral blood of patients with epithelial cancer.
MATERIALS AND METHODS
We analyzed the peripheral blood of 46 patients with gastric cancer who had undergone curative resection. The presence of CEA mRNA was serially monitored using RT-PCR (Preop, Post op 15 day, 2 months (m), 4 m, 6 m, 8 m, 10 m, 12 m). The clinical characteristics, serum CEA level and immunohistochemical staining of tumor tissue were also evaluated. Patients were followed up for 6 to 12 months.
RESULTS
There was no significant relationship seen between CEA mRNA RT-PCR positivity in the peripheral blood and sex, stage, serum CEA level or immunohistochemical staining for CEA antigen, During follow up,eight patients experienced recurrence; were positve for CEA mRNA RT-PCR recurrence was seen in 66.7% (6/9) of the patients who before clinical recurrence as compared to 5.4% (2/37) of patients who were negative (p=0.0002). Serial changes of CEA mRNA RT-PCR correlated with clinical recurrence; 100% in the positively converted group (3/3), 0% in the negatively converted group(0/18), 50% in all positive group (3/6) and 10.5% in all negative group (2/19) experienced recurrence, respectively.
CONCLUSION
RT-PCR analysis of CEA mRNA in the peripheral blood seems to be a promising tool for the early detection of micrometastatic circulating tumor cells in gastric cancer patients and may be useful in determining patients at high risk for recurrence. However, definitive correlation with recurrence certainly requires a longer follow up duration in further studies.

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Detection of Circulating Tumor Cells in Peripheral Blood by Reverse Transcriptase - polymerase Chain Reaction in Gastric Cancer Patients: H Kim, Y Y Lee, T J Jeong, I Y Choi, I S Kim, D S Han, Y C Jeon, J H Sohn, W G Park, H G Paik, H G Lee, Y S Nam, M J Ahn; J Korean Cancer Assoc. 2000;32(2):304-311.

Abstract PDF: PURPOSE
Cancer cells can be detected in bloods, lymph nodes or bone marrows by using reverse transcriptase-polymerase chain reaction (RT-PCR). We investigated to detect carcinoembryonic antigen (CEA) mRNA in peripheral blood by RT-PCR as a circulating tumor cell maker of gastric cancer patients.
MATERIALS AND METHODS
Gastric cancer patients were early gastric cancer with curative surgery (Group A, n=9), advanced gastric cancer with curative surgery (Group B, n 18) and relapsed or metastatic gastric cancer (Group C, n=13). RT-PCR was performed to detect CEA mRNA expression in the peripheral blood mononuclear cells and we used Colo 201 cells as a positive control.
RESULTS
Seventeen patients (42.5%) were positive for CEA mRNA, whereas all the nine normal subjects were negative. There were significant differences between group A and C (p=0.041), group B and C (p=0.001) and between patients underwent curative surgery and metastatic gastric cancer patients (p 0.001) but not between A and B (p 0.326) for the positive rate of CEA mRNA.
CONCLUSION
Large number of gastric cancer patients showed positive CEA mRNA in peripheral blood suggesting that gastric cancer cells can metastasize into blood at early stage.

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The Clinical Values of Metaplasia, p 53, c - erbB2 and CEA Expression in Gallbladder Carcinoma: Seok Mo Kim, Seong Hwan Kim, Jeong Hwan Chang, Sung chul Lim, Chae Hong Suh; J Korean Cancer Assoc. 1999;31(6):1261-1270.

Abstract PDF: PURPOSE
We evaluated the correlation between the carcinogenesis of gallbladder and the expression of lysozyme, p53, c-erbB2 and CEA in gallbladder lesions.
MATERIALS AND METHODS
Thirty cases of gallbladder lesions (containing 17 cases of GB carcinoma) were examined. We analyzed the clinicopathologic findings of the early (stage I & II) and advanced carcinoma (stage III, IV & V) and those of carcinoma with or without metaplasia in the tumor. We performed p53, c-erbB2 and CEA immunohistochemical staining and compared their findings with those of normal mucosa and preneoplastic lesions. We also performed lysozyme immunohistochemical staining and compared its finding with metaplastic and non-metaplastic lesions.
RESULTS
There are two distinct genetic pathways in gallbladder cacinogenesis and metaplastic carcinoma was more frequent than non-metaplastic carcinoma. Metaplasia of gallbladder did not reveal any difference of the clinicopathologic findings and depth of invasion (Nevin stage). Lysozyme expression was found in all metaplastic lesions but non-expression did not indicate non-metaplastic lesions. p53 mutations and c-erbB2 alterations may have a role in the carcinogenesis of gallbladder carcinomas, especially, in a late event, and in an early and late events, respectively. The correlation of p53 and c-erbB2 expressions was found but which did not indicate that the co-expression was needed in the carcinogenesis. CEA immunohistochemical staining may be helpful in the differential diagnosis of benign lesions and precancerous and cancerous lesions of the gallbladder.
CONCLUSION
These results suggest that p53 mutations and c-erbB2 alterations may have a role in the carcinogenesis of gallbladder carcinomas, especially, in a late event, and in an early and late events, respectively.

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Free Cancer Cell Detection in Peritoneal Cavitr of Gastric Cancer Patients by RT-PCR for CEA: See Young Kim, Jong Inn Lee, Nan Mo Moon, Nam Sun Paik, Dong Wook Choi, Ho Yoon Bang, Woo Chul Noh; J Korean Cancer Assoc. 1999;31(1):24-30.

Abstract PDF: PURPOSE
This study is aimed to evaluate the efficacy of a novel method (RT-PCR for CEA) to diagnose free cancer cells in peritoneal cavity of gastric cancer patients, which can be used as a indication of prophylactic treatment to prevent peritoneal recurrence after curative resection of gastric cancer.
MATERIALS AND METHODS
114 gastric adenocarcinoma patients were included for this study. With pellet of peritoneal washing fluid, cytology and RT-PCR for CEA were performed with specific primers.
RESULTS
Positive rate of PCR as a whole was 55.3% (63 cases); however, that of cytology was 15.8% (18 cases). Positive rate of PCR increased with depth of invasion of the lesion (p=0.026); however, that of cytology didn't (p=0.233). In early gastric cancer and seeding cases, PCR was not more sensitive than cytologic examination in detection of free cancer cell, but in pm, ss and si cancers, PCR was much more sensitive than cytology (p<0.001).
CONCLUSION
PCR was more sensitive to diagnose free cancer cells in peritoneal cavity of gastric cancer patients especially in pm, ss and si cancers than conventional cytologic examination, and it can be a good candidate of indication of prophylactic treatment to prevent peritoneal recurrence after curative resection.

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Prognostic Value of CEA and CA19 - 9 in Serum and Peritoneal Washing Fluid in Gastric Carcinoma: Sang Uk Han, Yong Kwan Cho, Seong Woo Hong, Young Ae Lim, Yun Sik Kwak, Myung Wook Kim; J Korean Cancer Assoc. 1998;30(5):869-878.

Abstract PDF: PURPOSE
The clinical significance of preoperative serum levels of CEA and CA19-9, levels of CEA and CA19-9 in peritoneal washing fluid and free cancer cells in peritoneal washing fluid in gastric cancer patients were evaluated in this study.
MATERIALS AND METHODS
Serum and peritoneal levels of CEA and CA19-9 and peritoneal washing cytology in 115 patients with gastric cancer were analyzed with respect to the prognostic factors using univariate and multivariate analysis.
RESULTS
Positive rate of serum CEA and CA19-9 was 16.5%, 13.0%. And that of peritoneal washing CEA, CA19-9 and cytology was 15.7%, 7.8% and 9.6%. A univariate analysis showed that tumor markets in serum and peritoneal washing fluid and peritoneal washing cytology had significant correlations with the progression of the tumors, and patients with positive serum or peritoneal tumor markers had poorer survival after operation than did the patients with negative tumor markers. But in a multivariate analysis showed that only peritoneal CA19-9 was an independent risk factor. And combination of these five markers provided rnore predictable prognostic informations in a multivariate analysis.
CONCLUSION
Combination of serum or peritoneal levels of CEA, CA19-9 and washing cytology appeared to be a useful marker for managing gastric cancer patients.

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The Comparative Study between Peripharal Venous Blood and Draining Venous Blood CEA Levels in Colorectal Cancer: Kyung Bum Lee, Eun Sook Lee, Young Chul Kim; J Korean Cancer Assoc. 1998;30(2):306-312.

Abstract PDF: PURPOSE
In colon cancer, CEA(carcinoembryonic antigen) has become one of the useful tools for the management of patients because the antigen has been found to be useful as a monitor for detection, staging, recurrence, determining the response to therapy, and estimating the prognosis or survival. Many investigators have been analyzing the peripheral CEA levels for these purpose. Correlation between CEA levels of peripheral and portal blood, and histopathologic variables, was examined in 92 patients. This study evaluates importance of draining vein CEA levels in sensitivity and specificity of the prognosis.
MATERIALS AND METHODS
In 92 patients, comparison between peripheral and draining venous blood CEA levels was performed in order to get better sensitivity and specificity and precise prognosis of CEA in colorectal cancer. Stage, tumor site, tumor emboli, lymph nodes, ascitic fluid cytology and differentiations were considered.
RESULTS
There was no significant difference in peripheral and draining venous blood CEA levels in these variables. CEA positive rate of peripheral and draining vein were 57% and 60%. It has statistically no significance. More elevated CEA levels of draining vein than peripheral levels was detected in Duke C comparison (p=0.013). And more elevated CEA levels was observed in more advanced stages(33%, 59%, 63%, 83%) in draining vein(p < or = 0.01).
CONCLUSION
The prognosis of elevated CEA level in draining venous blood CEA levels in advanced stage is significant in prediction of patients prognosis and degree of advanced cancers.

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The Cytotoxic Activity of Sterol Derivatives from Pulsatilla Chinensis Regal: Jin Won Hyun, Yong Man Yang, Min Sook Sung, Ha Sook Chang, Woo Hun Paik, Sam Sik Kang, Jae Gahb Park; J Korean Cancer Assoc. 1996;28(1):145-151.

Abstract PDF: In order to search for antineoplastic components from plants, cytotoxic activity against human carcinoma cell lines was measured in 266 extracts from 236 plants using the MTT (3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method. As a result, the root of Pulsatilla chinensis (Ranunculaceae), which has been used as an insecticide in oriental medicine, showed a cytotoxic effect. Its structure was determined to be a mixture of ￥a-sitosterol-3-O-glucoside and stigmasterol-3-O-glucoside (3:1). Its IC value was 26￥ig/ml against SNU-I stomach cancer cell line.

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Determination of Serum CEA Level in Primary Lung Cancer: Jin Hyuk Choi, Jung Hyun Chang, Soon Nam Lee, Eun Mi Nam, Ki Ryung Park, Sa Young Park, Hyo Jin Lee, Sung Min Cho, Young Sun Kim, Ka Eun Woo, Na Young Lee, Na Young Lee, Kwang Ho Kim; J Korean Cancer Assoc. 1996;28(2):281-286.

Abstract PDF: Background
The role of serum carcinoembryonic antigen(CEA) as a tumor marker in primary lung cancer remains unanswered. Several reports suggested that usefulness of serum CEA was limited to specific histologic types or clinical situations. Methods: Serum levels of CEA were determined in 126 patients with primary lung cancer and its correlation with clinico-pathologic characteristics was investigated. Results: Serum CEA was positive (defined as>5ng/ml) in 71 patients(56.3%). The positivity of serum CEA was significantly higher in adenocarcinoma(72.3%) than that in squamous cell carcinoma(46.5%) and small cell carcinoma(44.0%) (p=0.025). There was no significant difference in positivity of CEA according to sex and stages. Conelueion: Serum CEA does not seem to be standard tumor marker of primary lung cancer. However, it could be useful as prognostic factor or monitor of treatment results, especially in adenocarcinoma.

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Determination of Preoperative Serum CEA Level in Curativeal Resected Gastric Cancer: Jin Hyuk Choi, Sun Young Lee, Kang Sup Shim, Hye Young Son, Ki Youl Seo, Jong Seon Kim, Jin Ah Park, Eun Soon Hong, Hyo Jeong Kim, Su Young Park, Min Gyeu Hwang, Kang Sup Shim; J Korean Cancer Assoc. 1996;28(6):1050-1055.

Abstract PDF: Background
Although the role of serum carcinoembryonic antigen(CEA) as a tumor marker in gastric cancer remains unanswered, several reports suggested the usefulness of serum CEA as prognostic factor or indicator of recurrence. Methods: Preoperative serum levels of CEA were determined in 79 patients with curatively resected gastric cancer and its correlation with clinicopathologic characteristics was investigated. Results: Serum CEA was positive(defined as>5ng/ml) in 16 patients(20.3%). The mean age of CEA positive group(62.9¡¾7.5 years) was significantly older than that of the negative group(53.2¡¾12.7 years)(p=0.005), and Borrmann type III cases were more frequent in CEA positive group(56.3% vs. 19.0%)(p=0.026). There were no significant differences between two groups in other clinicopathologic characteristics, including tumor size, tumor location, differentiation of tumor, and stages. Conclusion: Serum CEA does not seem to be standard. tumor marker of gastric cancer, in terms of screening or diagnosis. However, it could be useful as prognostic factor or for early detection of recurrence in curatively resected gaxtric cancer

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