Simultaneous in vitro drug sensitivity testing on tumors from different sites in the same patient

Abstract

A human tumor cloning assay was used to analyze drug sensitivity profiles for 99 pairs of tumor samples taken simultaneously from the same patient. These pairs included two areas of the same primary (12 pairs), primary tumor versus metastasis (29 pairs), and metastasis versus metastasis (45 pairs). In addition, to assess variability in the culture and sensitivity techniques, 13 specimens were divided equally and processed twice. One hundred fourteen evaluable drug sensitivity tests were performed on the specimen pairs. Drug sensitivity profiles for the same specimen processed twice demonstrated good agreement (P = 0.03). Sensitivity profiles from two different areas of the same primary were also quite similar (P = 0.002). However, when one sampled a primary tumor and its metastasis for drug sensitivity testing, the agreement (in terms of percent survival) was poor (P = 0.84). Agreement was also poor for drug sensitivity profiles of one metastasis versus another metastasis (P = 0.39). This heterogeneity in drug sensitivity profiles of primary versus metastasis and of metastasis versus metastasis could account for some of the false positives and false negatives noted in clinical correlation trials with the cloning assay. It may also have implications for adjuvant treatment programs where chemosensitivity of the primary tumor can be determined, but will probably not be predictive for chemosensitivity of the micrometastases.

Malignancy through cooperation: an evolutionary game theory approach

“…The discovery that only certain cells can produce growth factors that the tumour as a whole needs, explains in homogeneous distribution of proteins in tumour tissue observed after immunohistochemical staining . The demonstrated need for tumour cell cooperation across phenotypes verifies the importance of transferring some tumour‐derived cell lines at high concentrations . Because of the difficulty of studying paracrine signalling mechanisms , results of this study have no current experimental comparison.…”

The establishment of sublines with opposite chemosensitivity from a patient with pulmonary large cell carcinoma and the implementation of treatment based on tumor heterogeneity

“…Although there are a few reports focusing on the heterogeneity of chemosensitivity in the same tumor, 3,10 to the best of our knowledge this is the first case to be reported in which sublines with contrasting opposite sensitivity to anticancer drugs were estab- Accordingly, the disease was diagnosed as pulmonary cancer following a relatively benign course; however, substrains with different growth patterns were observed in the primary culture, and rapid growth was noted in vitro.…”

“…3,4 The isolation culture of various sublines with different growth patterns in the early stage of subculture and examination of their sensitivities enables comprehensive treatment that Reprint requests to: S. Kobayashi (Received for publication on Sept. 21, 1998; accepted on Mar. Thus, meticulous treatment that takes such diversity into account is considered essential to achieve breakthroughs in current cancer chemotherapy.…”

c-myc Amplification and Enhancement of Sensitivity to Cytosine Arabinoside: An In Vitro and In Vivo Study on Four Sublines Established from a Pulmonary Adenocarcinoma

“…3,4 This tumor heterogeneity of human cancers is considered a major reason for the difficulty in predicting the prognosis of patients with early-stage cancers and in treating patients with advanced cancers. Therefore, more accurate diagnostic indicators and meticulous treatment strategies taking tumor heterogeneity into account are considered essential to achieve breakthroughs in current cancer diagnosis and therapy.…”