Trop-2 Therapy in Metastatic Triple-Negative Breast Cancer in Italy: Clinical Opportunity and Regulatory Pitfalls

Bravaccini, Sara; Maltoni, Roberta

doi:10.3390/jpm11111211

Cited by 13 publications

(6 citation statements)

References 32 publications

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“…A large proportion of patients in both groups was ER and PR positive, whereas 506 patients in the DianaWeb cohort (34.0%) and 90 patients in the DianaWeb sub-cohort (40.2%) were HER2 positive. Triple-negative phenotype accounted for 23.7% of the whole DianaWeb cohort and 28.1 of the pandemic sub-cohort, a proportion higher than that reported for the Italian population (15–20%) (Supplementary Table 1 ) [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

How the COVID-19 pandemic has affected eating habits and physical activity in breast cancer survivors: the DianaWeb study

et al. 2022

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Purpose Breast cancer (BC) survivors are increasingly interested in learning about healthy lifestyles to reduce the risk of BC recurrence and mortality. The DianaWeb study, a community-based participatory research, offers BC patients a specific interactive website to help them in adopting and maintain correct lifestyles, in line with World Cancer Research Fund recommendations. However, to limit the spread of the COVID-19 pandemic, most countries introduced restrictions which, inevitably, caused sudden lifestyle changes. The current study aimed at evaluating changes in lifestyle in BC survivors before, during, and after the first two waves of the COVID-19 pandemic. Methods We used data of 224 BC cancer survivors enrolled in the DianaWeb study. We evaluated the adherence to physical activity (PA) guidelines, to Mediterranean diet (MD), and WCRF recommendations, at baseline, during and after the first two waves of the COVID-19 pandemic. We estimated the association between PA, MD, and WCRF adherence with sociodemographic characteristics, years from enrolment in the DianaWeb study, and type of breast cancer. Results As expected, during confinement periods, we observed a significant decrease in walking activity and in the percentage of patients performing vigorous PA. In post-quarantine, total weekly energy expenditure increased significantly. BC patients participating in the DianaWeb study for more than 3 years were more likely to be more active. There were no changes in MD and WCRF adherence. Conclusions Our results show that the proposed interactive website was useful in achieving durable lifestyle changes, that have not been undermined either during the COVID-19 pandemic. Implications for Cancer Survivors Patient education is essential for guiding BC survivors toward improving their health outcomes; therefore, an interactive website like the one proposed by the DianaWeb study may be useful to improve healthy lifestyles.

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Section: Resultsmentioning

confidence: 99%

How the COVID-19 pandemic has affected eating habits and physical activity in breast cancer survivors: the DianaWeb study

et al. 2022

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“…In breast cancer, TrkA/CD44v3 complex formation is inversely correlated with PR expression and is associated with TN status. In this latter subtype, only sacituzumab govitecam passed through drug process development and was recently approved by the Food and Drug Administration and European Medecines Agency [ 36 ]. Similar to sacituzumab govitecam, our fundamental discovery may highly impact the development of new treatments based on TNBC-specific membrane receptor targeting.…”

Section: Discussionmentioning

confidence: 99%

Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells

Trouvilliez

Cicero

Lévêque

et al. 2022

J Exp Clin Cancer Res

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Background CD44 is a multifunctional membrane glycoprotein. Through its heparan sulfate chain, CD44 presents growth factors to their receptors. We have shown that CD44 and Tropomyosin kinase A (TrkA) form a complex following nerve growth factor (NGF) induction. Our study aimed to understand how CD44 and TrkA interact and the consequences of inhibiting this interaction regarding the pro-tumoral effect of NGF in breast cancer. Methods After determining which CD44 isoforms (variants) are involved in forming the TrkA/CD44 complex using proximity ligation assays, we investigated the molecular determinants of this interaction. By molecular modeling, we isolated the amino acids involved and confirmed their involvement using mutations. A CD44v3 mimetic peptide was then synthesized to block the TrkA/CD44v3 interaction. The effects of this peptide on the growth, migration and invasion of xenografted triple-negative breast cancer cells were assessed. Finally, we investigated the correlations between the expression of the TrkA/CD44v3 complex in tumors and histo-pronostic parameters. Results We demonstrated that isoform v3 (CD44v3), but not v6, binds to TrkA in response to NGF stimulation. The final 10 amino acids of exon v3 and the TrkA H112 residue are necessary for the association of CD44v3 with TrkA. Functionally, the CD44v3 mimetic peptide impairs not only NGF-induced RhoA activation, clonogenicity, and migration/invasion of breast cancer cells in vitro but also tumor growth and metastasis in a xenograft mouse model. We also detected TrkA/CD44v3 only in cancerous cells, not in normal adjacent tissues. Conclusion Collectively, our results suggest that blocking the CD44v3/TrkA interaction can be a new therapeutic option for triple-negative breast cancers.

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“…In tumors expressing Trop2, the antibody component of sacituzumab govitecan would be able to recognize the surface protein and bind to it, resulting in the internalization of the ADC through the formation of an endosome (Fig. 5b) (Bravaccini and Maltoni 2021). The subsequent acidification of the endosome results in the cleavage of the linker, thereby releasing the drug, SN-38, into the cytoplasm upon the fusion of the endosome with the lysosome (Fig.…”

Section: Mechanism Of Action Of Sacituzumab Govitecanmentioning

confidence: 99%

“…As a topoisomerase I inhibitor, SN-38 prevents the repair of single-strand breaks in DNA, resulting in DNA damage and cell death thereafter (Fig. 5b) (Bravaccini and Maltoni 2021). Therefore, the mechanism of action of an ADC is dependent on the selection of an antigen that is highly expressed in cancer tissue while having reduced expression in the surrounding normal tissue (Nagayama et al 2020).…”

Section: Mechanism Of Action Of Sacituzumab Govitecanmentioning

confidence: 99%

Triple negative breast cancer: approved treatment options and their mechanisms of action

Mandapati

Lukong

2022

J Cancer Res Clin Oncol

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Purpose Breast cancer, the most prevalent cancer worldwide, consists of 4 main subtypes, namely, Luminal A, Luminal B, HER2-positive, and Triple-negative breast cancer (TNBC). Triple-negative breast tumors, which do not express estrogen, progesterone, and HER2 receptors, account for approximately 15-20% of breast cancer cases. The lack of traditional receptor targets contributes to the heterogenous, aggressive, and refractory nature of these tumors, resulting in limited therapeutic strategies. Methods Chemotherapeutics such as taxanes and anthracyclines have been the traditional go to treatment regimens for TNBC patients. Paclitaxel, docetaxel, doxorubicin, and epirubicin have been longstanding, Food and Drug Administration (FDA)-approved therapies against TNBC. Additionally, the FDA approved PARP inhibitors such as olaparib and atezolizumab to be used in combination with chemotherapies, primarily to improve their efficiency and reduce adverse patient outcomes. The immunotherapeutic Keytruda was the latest addition to the FDA-approved list of drugs used to treat TNBC. Results The following review aims to elucidate current FDA-approved therapeutics and their mechanisms of action, shedding a light on the various strategies currently used to circumvent the treatment-resistant nature of TNBC cases. Conclusion The recent approval and use of therapies such as Trodelvy, olaparib and Keytruda has its roots in the development of an understanding of signaling pathways that drive tumour growth. In the future, the emergence of novel drug delivery methods may help increase the efficiency of these therapies whiel also reducing adverse side effects.

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Trop-2 Therapy in Metastatic Triple-Negative Breast Cancer in Italy: Clinical Opportunity and Regulatory Pitfalls

Cited by 13 publications

References 32 publications

How the COVID-19 pandemic has affected eating habits and physical activity in breast cancer survivors: the DianaWeb study

How the COVID-19 pandemic has affected eating habits and physical activity in breast cancer survivors: the DianaWeb study

Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells

Triple negative breast cancer: approved treatment options and their mechanisms of action

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