Unexpected Growth-Promoting Effect of Oxaliplatin in Excision Repair Cross-Complementation Group 1 Transfected Human Colon Cancer Cells

Jordheim, Lars Petter; Chettab, Kamel; Cros‐Perrial, Emeline; Matera, Eva–Laure; Dumontet, Charles

doi:10.1159/000491587

Cited by 9 publications

(8 citation statements)

References 22 publications

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“…As indicated by the T/C >1 (Figure 8d), oxaliplatin promoted the growth of tumor from 9 th to 18 th days. Although, at this stage, we don't have an explanation for this unclassical behavior, we noted that a similar observation was reported earlier for oxaliplatin in a HCT116 tumor xenograft [33] …”

Section: Resultssupporting

confidence: 77%

A Rationally Designed Bimetallic Platinum (II)‐Ferrocene Antitumor Agent Induces Non‐Apoptotic Cell Death and Exertsin VivoEfficacy

Gadre

Manikandan

Duari

et al. 2022

Chemistry A European J

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Despite phenomenal clinical success, the efficacy of platinum anticancer drugs is often compromised due to inherent and acquired drug resistant phenotypes in cancers. To circumvent this issue, we designed two heterobimetallic platinum (II)‐ferrocene hybrids that display multi‐pronged anticancer action. In cancer cells, our best compound, 2, platinates DNA, produces reactive oxygen species, and has nucleus, mitochondria, and endoplasmic reticulum as potential targets. The multi‐modal mechanism of action of these hybrid agents lead to non‐apoptotic cell death induction which enables circumventing apoptosis resistance and significant improvement in platinum cross resistance profile. Finally, in addition to describing detail mechanistic insights, we also assessed its stability in plasma and demonstrate anticancer efficacy in an in vivo A2780 xenograft model. Strikingly, compared to oxaliplatin, our compound displays better tolerability, safety profile and efficacy in vivo.

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Section: Resultssupporting

confidence: 77%

A Rationally Designed Bimetallic Platinum (II)‐Ferrocene Antitumor Agent Induces Non‐Apoptotic Cell Death and Exertsin VivoEfficacy

Gadre

Manikandan

Duari

et al. 2022

Chemistry A European J

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“…Eventually it was discovered that Trop-2 may modulate the effects of certain chemotherapeutic regimens. For example, Jordheim et al have suggested that Trop-2 is potentially involved in a paradoxical growth-promoting effect of oxaliplatin, a platinum-based chemotherapeutic, when administered to a xenograft model of HCT-116 human colon cancer cells 38. Moreover, Zhang et al found that curcumin treatment decreases Trop-2 expression and that downregulation of Trop-2 expression suppressed cell proliferation and mobility and increased apoptosis in bladder cancer cells 39…”

Section: Basic Science Backgroundmentioning

confidence: 99%

<p>Targeting Trop-2 in solid tumors: future prospects</p>

Zaman¹,

Jadid²,

Denson³

et al. 2019

OTT

114

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Trop-2 is a transmembrane glycoprotein that is upregulated in all cancer types independent of baseline levels of Trop-2 expression. Trop-2 is an ideal candidate for targeted therapeutics due to it being a transmembrane protein with an extracellular domain overexpressed on a wide variety of tumors as well as its upregulated expression relative to normal cells. As a result, several Trop-2-targeted therapeutics have recently been developed for clinical use, such as anti-Trop-2 antibodies and Trop-2-targeted antibody–drug conjugates (ADC). Subsequently, multiple early-phase clinical trials have demonstrated safety and clinical benefit of Trop-2-based ADCs across multiple tumor types. This includes clinical benefit and tolerability in tumor types with limited treatment options, such as triple-negative breast cancer, platinum-resistant urothelial cancer, and small-cell lung cancer. In this review, we elaborate on all clinical trials involving Trop-2.

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“…Human trophoblast cell surface antigen 2 (TROP2), also called tumor-associated calcium signal transduction-2 (TACSTD-2), is a surface glycoprotein encoded by TACSTD that has extracellular domains, a single transmembrane domain, and a short tail [ 4 , 5 ]. TROP2 is overexpressed in many human cancers, including ovarian [ 6 , 7 ], gastric [ 8 , 9 ], colorectal [ 10 ], pancreatic [ 11 ], and laryngeal cancers [ 12 ]. Inhibiting TROP2 expression has shown promise in clinical applications [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation

Zhang

Gao

et al. 2020

BMC Cancer

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Background: Trophoblast cell surface antigen 2 (TROP2) is overexpressed in many squamous cell carcinomas and promotes tumor development and invasion. The association between TROP2 expression and occurrence and development of oral squamous cell carcinoma (OSCC) remains to be understood. Methods: We investigated the role of TROP2 in OSCC patients using a combination of biophysical approaches. A total of 108 OSCC patient specimens with varying degrees of differentiation were subjected to hematoxylin and eosin staining, immunohistochemistry, Kaplan-Meier survival curve analysis, and atomic force microscopy to analyze TROP2 expression, morphology, and mechanical properties of OSCC tissues. Results: TROP2 was overexpressed in 34% of poorly differentiated OSCC samples. High levels of TROP2 were associated with 10.2% survival rate lower than 45.4% and patient age (odds ratio [OR] = 0.437, P = 0.039, 95% confidence interval [CI, 0.198-0.966]), tumor size (OR = 13.148, P = 0.000, 95% CI [5.060-34.168]), and TNM stage (OR = 0.141, P = 0.000, 95% CI [0.082-0.244]). Average surface roughness of low, medium, and highly differentiated OSCC tissues were 448.9 ± 54.8, 792.7 ± 83.6, and 993.0 ± 104.3 nm, respectively. The Pearson coefficient revealed a negative association between tumor stiffness and TROP2 expression (r = − 0.84, P < 0.01). Conclusion: Overexpression of TROP2 negatively associated with patient survival, degree of tumor differentiation, and tissue mechanics. Taken together, our findings demonstrated that TROP2 may be an indicator of OSCC differentiation leading to the altered mechanical properties of OSCC tissues.

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Unexpected Growth-Promoting Effect of Oxaliplatin in Excision Repair Cross-Complementation Group 1 Transfected Human Colon Cancer Cells

Cited by 9 publications

References 22 publications

A Rationally Designed Bimetallic Platinum (II)‐Ferrocene Antitumor Agent Induces Non‐Apoptotic Cell Death and Exertsin VivoEfficacy

A Rationally Designed Bimetallic Platinum (II)‐Ferrocene Antitumor Agent Induces Non‐Apoptotic Cell Death and Exertsin VivoEfficacy

<p>Targeting Trop-2 in solid tumors: future prospects</p>

Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation

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