Metronomic Chemotherapy

Cazzaniga, Marina Elena; Cordani, Nicoletta; Capici, Serena; Cogliati, Viola; Riva, Francesca; Cerrito, Maria Grazia

doi:10.3390/cancers13092236

Cited by 59 publications

(67 citation statements)

References 130 publications

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“…As continuous drug injection is clinically impossible owing to the very harmful side effects on normal cells, it is necessary to assess the efficacy of MTD, LDC, and CS methods comparatively. Despite promising preliminary results showed in different studies, only limited data has been available for a long time regarding the right dose of the different drugs to be used in the metronomic administration 44 . In many ways, development in MC and CS allows for the utilization of computational oncology at the bedside, since the optimization of an MC or CS regimen is largely achievable only with the help of modeling before clinical trials 16 , 45 .…”

Section: Discussionmentioning

confidence: 99%

Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

Kashkooli

Soltani

2021

Sci Rep

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The development of an in silico approach that evaluates and identifies appropriate treatment protocols for individuals could help grow personalized treatment and increase cancer patient lifespans. With this motivation, the present study introduces a novel approach for sequential treatment cycles based on simultaneously examining drug delivery, tumor growth, and chemotherapy efficacy. This model incorporates the physical conditions of tumor geometry, including tumor, capillary network, and normal tissue assuming real circumstances, as well as the intravascular and interstitial fluid flow, drug concentration, chemotherapy efficacy, and tumor recurrence. Three treatment approaches—maximum tolerated dose (MTD), metronomic chemotherapy (MC), and chemo-switching (CS)—as well as different chemotherapy schedules are investigated on a real tumor geometry extracted from image. Additionally, a sensitivity analysis of effective parameters of drug is carried out to evaluate the potential of using different other drugs in cancer treatment. The main findings are: (i) CS, MC, and MTD have the best performance in reducing tumor cells, respectively; (ii) multiple doses raise the efficacy of drugs that have slower clearance, higher diffusivity, and lower to medium binding affinities; (iii) the suggested approach to eradicating tumors is to reduce their cells to a predetermined rate through chemotherapy and then apply adjunct therapy.

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Section: Discussionmentioning

confidence: 99%

Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

Kashkooli

Soltani

2021

Sci Rep

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“…IL-17 and its downstream factor, granulocyte colonystimulating factor (G-CSF), are the leading players of inflammation; it has been reported that a high level of IL-17 induces cells to produce a paracrine network that confers resistance to anti-VEGF therapy. Serum G-CSF levels in CRC patients are higher than those in healthy volunteers and are associated with the stage of tumor progression [154,155] .…”

Section: Resistance To Anti-angiogenic Therapymentioning

confidence: 99%

Emerging actionable targets to treat therapy-resistant colorectal cancers

Grassilli¹,

Cerrito²

2022

CDR

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In the last two decades major improvements have been reached in the early diagnosis of colorectal cancer (CRC) and, besides chemotherapy, an ampler choice of therapeutic approaches is now available, including targeted and immunotherapy. Despite that, CRC remains a “big killer” mainly due to the development of resistance to therapies, especially when the disease is diagnosed after it is already metastatic. At the same time, our knowledge of the mechanisms underlying resistance has been rapidly expanding which allows the development of novel therapeutic options in order to overcome it. As far as resistance to chemotherapy is concerned, several contributors have been identified such as: intake/efflux systems upregulation; alterations in the DNA damage response, due to defect in the DNA checkpoint and repair systems; dysregulation of the expression of apoptotic/anti-apoptotic members of the BCL2 family; overexpression of oncogenic kinases; the presence of cancer stem cells; and the composition of the tumoral microenvironment and that of the gut microbiota. Interestingly, several mechanisms are also involved in the resistance to targeted and/or immunotherapy. For example, overexpression and/or hyperactivation and/or amplification of oncogenic kinases can sustain resistance to targeted therapy whereas the composition of the gut microbiota, as well as that of the tumoral niche, and defects in DNA repair systems are crucial for determining the response to immunotherapy. In this review we will make an overview of the main resistance mechanisms identified so far and of the new therapeutic approaches to overcome it.

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“…The concept of MC, and its therapeutic use, have been extensively reviewed [19][20][21][22][23]25] as regards the treatment of breast cancer [34,35], non-small-cell lung cancer (NSCLC) [36], and high-risk pediatric malignancies [37]. A systematic review on MC compiles the clinical experience in different cancers such as breast, castration-resistant prostate, ovarian, glial, renal, lung, gastrointestinal, hepatocellular, multiple myeloma, melanoma, and head and neck [38].…”

Section: Metronomic Chemotherapy: a Multimodal Therapymentioning

confidence: 99%

“…As such, understanding these complex and multifaceted interactions could help improve the selection of drug combinations and schedules and reduce resistance to anticancer drugs. MC has become a new treatment option [22] that can be applied to chemotherapy, radiotherapy, and biotherapy [23]. In this regard, nanotherapy offers smartly targeted nanoparticles with modifiable properties to target components of the tumor microenvironment and could therefore be a good addition to MC [24].…”

Section: Introductionmentioning

confidence: 99%

Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment

Muñoz

Girotti

Hileeto

et al. 2021

Cancers

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The concept of cancer as a systemic disease, and the therapeutic implications of this, has gained special relevance. This concept encompasses the interactions between tumor and stromal cells and their microenvironment in the complex setting of primary tumors and metastases. These factors determine cellular co-evolution in time and space, contribute to tumor progression, and could counteract therapeutic effects. Additionally, cancer therapies can induce cellular and molecular responses in the tumor and host that allow them to escape therapy and promote tumor progression. In this study, we describe the vascular network, tumor-infiltrated immune cells, and cancer-associated fibroblasts as sources of heterogeneity and plasticity in the tumor microenvironment, and their influence on cancer progression. We also discuss tumor and host responses to the chemotherapy regimen, at the maximum tolerated dose, mainly targeting cancer cells, and a multimodal metronomic chemotherapy approach targeting both cancer cells and their microenvironment. In a combination therapy context, metronomic chemotherapy exhibits antimetastatic efficacy with low toxicity but is not exempt from resistance mechanisms. As such, a better understanding of the interactions between the components of the tumor microenvironment could improve the selection of drug combinations and schedules, as well as the use of nano-therapeutic agents against certain malignancies.

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Metronomic Chemotherapy

Cited by 59 publications

References 130 publications

Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

Evaluation of solid tumor response to sequential treatment cycles via a new computational hybrid approach

Emerging actionable targets to treat therapy-resistant colorectal cancers

Metronomic Anti-Cancer Therapy: A Multimodal Therapy Governed by the Tumor Microenvironment

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