1. Intratumoral Treatment in Lung Cancer: Is It Time to Move Towards Clinical Practice?
- Author
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Pagliari, Gabriele Giuseppe, Colonese, Francesca, Canova, Stefania, Abbate, Maria Ida, Sala, Luca, Petrella, Francesco, Clementi, Thoma Dario, and Cortinovis, Diego Luigi
- Abstract
Simple Summary: The therapeutic strategies of NSCLC focus on systemic strategies, mainly chemotherapy and immunotherapy. Unfortunately, cancer has some aces up it's sleeve, in particular the tumoral microenvironment. An intratumoral strategy can be useful to overcome cancer's shelters. Some intratumoral strategies have been analyzed and proved during the last decades, including a treatment based on "classical" antiblastic agents, immunotherapy, and immunomodulating agents, which can be administered by direct injection, inhalation, and intrapleuraly. Other treatments take advantage of ablation techniques, including photodynamic and thermal. Moreover, it is possible to evaluate the use of electric fields, a promising technique, and brachytherapy, a consolidated one. Finally, nanoparticles are interesting and useful both for their direct activity and for their carrier role. Each intratumoral strategy should be chosen based on setting, metastasis status, cancer type, and patient features, etc. Furthermore, the evaluation of a combined approach is fundamental, because intratumoral and systemic strategies together can overcome the other's limitations and mutually enhance one another in order to become more efficient tools in the anticancer war. According to a modern view, cancer no longer follows a purely mechanistic model. Rather, a tumor is conceived as a more complex structure, composed of cancer cells, the activities of which may interact and reshape the so-called tumor microenvironment (TME), leading to preservation of specific tumoral niches and promoting the survival of tumoral stem cells. Background/Objective: Therapeutic strategies must deal with this unique cancer architecture in the near future by widening their range of activities outside the cancer cells and rewiring a TME to ensure it is hostile to cancer growth. Therefore, an intratumoral therapeutic strategy may open the door to a new type of anticancer activity, one that directly injures the tumoral structure while also eliciting an influence on the TME through local and systemic immunomodulation. This review would like to assess the current situation of intratumoral strategies and their clinical implications. Methods We analyzed data from phase I, II, and III trials, comprehensive reviews and relevant clinical and preclinical research, from robust databases, like PUBMED, EMBASE, Cochrane Library, and clinicaltrials.gov. Results: Intratumoral strategies can be quite variable. It is possible the injection and inhalation of traditional antiblastic agents or immunomodulant agents, or intrapleural administration. Ablation strategy is available, both thermal and photodynamic method. Moreover, TTfields and NPs are analyzed and also brachytherapy is mentioned. Intratumoral therapy can find space in "adjuvant"/perioperative or metastatic settings. Finally, intratumoral strategies allow to synergize their activities with systemic therapies, guaranteeing better local and systemic disease control. Conclusions: Intratumoral strategies are overall promising. Antiblastic/immunomodulant injection and NPs use are especially interesting and intriguing. But, there is generally a lack of phase II and III trials, in particular NPs use need additional experimentation and clinical studies. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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