Comparison of Drugs Used for Adjuvant and Metastatic Therapy of Colon, Breast, and Non–Small Cell Lung Cancers

Parsons, Scott; Maldonado, Edward; Prasad, Vinay

doi:10.1001/jamanetworkopen.2020.2488

Cited by 23 publications

(20 citation statements)

References 23 publications

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“…Among the most used chemotherapeutic drugs, approved as first- and second-line adjuvants in CRC, are 5-FU, irinotecan (CPT-11), OXA, capecitabine, and leucovorin[ 97 , 98 ]. Depending on the CRC subtype, these drugs are also used in combination with monoclonal antibodies, such as bevacizumab or cetuximab[ 5 ].…”

Section: Role Of β-Catenin and The Tme In The Chemoresistance Of Crcmentioning

confidence: 99%

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

Díaz¹,

Martín²,

Gentili³

2022

WJG

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Colorectal cancer (CRC) continues to be one of the main causes of death from cancer because patients progress unfavorably due to resistance to current therapies. Dysregulation of the Wnt/β-catenin pathway plays a fundamental role in the genesis and progression of several types of cancer, including CRC. In many subtypes of CRC, hyperactivation of the β-catenin pathway is associated with mutations of the adenomatous polyposis coli gene. However, it can also be associated with other causes. In recent years, studies of the tumor microenvironment (TME) have demonstrated its importance in the development and progression of CRC. In this tumor nest, several cell types, structures, and biomolecules interact with neoplastic cells to pave the way for the spread of the disease. Cross-communications between tumor cells and the TME are then established primarily through paracrine factors, which trigger the activation of numerous signaling pathways. Crucial advances in the field of oncology have been made in the last decade. This Minireview aims to actualize what is known about the central role of the Wnt/β-catenin pathway in CRC chemoresistance and aggressiveness, focusing on cross-communication between CRC cells and the TME. Through this analysis, our main objective was to increase the understanding of this complex disease considering a more global context. Since many treatments for advanced CRC fail due to mechanisms involving chemoresistance, the data here exposed and analyzed are of great interest for the development of novel and effective therapies.

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Section: Role Of β-Catenin and The Tme In The Chemoresistance Of Crcmentioning

confidence: 99%

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

Díaz¹,

Martín²,

Gentili³

2022

WJG

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“…In routine clinical practice and outside of clinical trials, these drugs are administered largely based on primary tumor biopsies in non-metastatic breast cancer. The limited success of this predominant treatment paradigm in the adjuvant-curative setting is well known and has recently been illuminated in a study by Parsons et al (2020) , which found that of 14 drugs recommended and used in the metastatic setting, only one (gefitinib in non-small cell lung cancer) was found to yield survival benefit for early-stage cancers.…”

Section: Clinical Backgroundmentioning

confidence: 99%

“…Currently, only 34.8% of drugs used in the metastatic setting are endorsed for adjuvant treatment for breast cancer, colorectal cancer or non-small cell lung cancer ( Parsons et al, 2020 ). Partially explained by more rigorous criteria for drug approval and registration in early-stage disease, the observed lack in efficacy argues against a simple correlation and indicates fundamental difference in the biology of micrometastatic vs. macrometastatic disease, with the former not adequately targeted by reutilized drug application.…”

Section: Clinical Backgroundmentioning

confidence: 99%

Clinical and Biological Aspects of Disseminated Tumor Cells and Dormancy in Breast Cancer

Ring

Spataro

Wicki

et al. 2022

Front. Cell Dev. Biol.

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Progress in detection and treatment have drastically improved survival for early breast cancer patients. However, distant recurrence causes high mortality and is typically considered incurable. Cancer dissemination occurs via circulating tumor cells (CTCs) and up to 75% of breast cancer patients could harbor micrometastatses at time of diagnosis, while metastatic recurrence often occurs years to decades after treatment. During clinical latency, disseminated tumor cells (DTCs) can enter a state of cell cycle arrest or dormancy at distant sites, and are likely shielded from immune detection and treatment. While this is a challenge, it can also be seen as an outstanding opportunity to target dormant DTCs on time, before their transformation into lethal macrometastatic lesions. Here, we review and discuss progress made in our understanding of DTC and dormancy biology in breast cancer. Strides in our mechanistic insights of these features has led to the identification of possible targeting strategies, yet, their integration into clinical trial design is still uncertain. Incorporating minimally invasive liquid biopsies and rationally designed adjuvant therapies, targeting both proliferating and dormant tumor cells, may help to address current challenges and improve precision cancer care.

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“…This is mainly due to the emergence of CRC patients under 50 years old and the appearance of new tumors subtypes that have a refractory response to the usual therapy[ 5 ]. Currently, two of the chemotherapeutic agents approved as first and second-line palliative drugs in CRC are oxaliplatin (OXA) and irinotecan (CPT-11)[ 6 , 7 ]. However, more than half of patients with stage II/III disease who underwent surgery and were treated with these drugs relapsed and died[ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Involvement of Met receptor pathway in aggressive behavior of colorectal cancer cells induced by parathyroid hormone-related peptide

Díaz¹,

Carriere²,

Gigola³

et al. 2022

WJG

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BACKGROUND Parathyroid hormone-related peptide (PTHrP) plays a key role in the development and progression of many tumors. We found that in colorectal cancer (CRC) HCT116 cells, the binding of PTHrP to its receptor PTHR type 1 (PTHR1) activates events associated with an aggressive phenotype. In HCT116 cell xenografts, PTHrP modulates the expression of molecular markers linked to tumor progression. Empirical evidence suggests that the Met receptor is involved in the development and evolution of CRC. Based on these data, we hypothesized that the signaling pathway trigged by PTHrP could be involved in the transactivation of Met and consequently in the aggressive behavior of CRC cells. AIM To elucidate the relationship among PTHR1, PTHrP, and Met in CRC models. METHODS For in vitro assays, HCT116 and Caco-2 cells derived from human CRC were incubated in the absence or presence of PTHrP (1-34) (10 -8 M). Where indicated, cells were pre-incubated with specific kinase inhibitors or dimethylsulfoxide, the vehicle of the inhibitors. The protein levels were evaluated by Western blot technique. Real-time polymerase chain reaction (RT-qPCR) was carried out to determine the changes in gene expression. Wound healing assay and morphological monitoring were performed to evaluate cell migration and changes related to the epithelial-mesenchymal transition (EMT), respectively. The number of viable HCT116 cells was counted by trypan blue dye exclusion test to evaluate the effects of irinotecan (CPT-11), oxaliplatin (OXA), or doxorubicin (DOXO) with or without PTHrP. For in vivo tests, HCT116 cell xenografts on 6-wk-old male N:NIH (S)_nu mice received daily intratumoral injections of PTHrP (40 μg/kg) in 100 μL phosphate-buffered saline (PBS) or the vehicle (PBS) as a control during 20 d. Humanitarian slaughter was carried out and the tumors were removed, weighed, and fixed in a 4% formaldehyde solution for subsequent treatment by immunoassays. To evaluate the expression of molecular markers in human tumor samples, we studied 23 specimens obtained from CRC patients which were treated at the Hospital Interzonal de Graves y Agudos Dr. José Penna (Bahía Blanca, Buenos Aires, Argentina) and the Hospital Provincial de Neuquén (Neuquén, Neuquén, Argentina) from January 1990 to December 2007. Seven cases with normal colorectal tissues were assigned to the control group. Tumor tissue samples and clinical histories of patients were analyzed. Paraffin-embedded blocks from primary tumors were reviewed by hematoxylin-eosin staining technique; subsequently, representative histological samples were selected from each patient. From each paraffin block, tumor sections were stained for immunohistochemical detection. The statistical significance of differences was analyzed using proper statistical analysis. The results were considered statistically significant at P < 0.0...

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Comparison of Drugs Used for Adjuvant and Metastatic Therapy of Colon, Breast, and Non–Small Cell Lung Cancers

Cited by 23 publications

References 23 publications

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

Clinical and Biological Aspects of Disseminated Tumor Cells and Dormancy in Breast Cancer

Involvement of Met receptor pathway in aggressive behavior of colorectal cancer cells induced by parathyroid hormone-related peptide

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