Chemotherapy as an Adjuvant to Surgery for Colorectal Cancer

Lawrence, Walter; Terz, José J.; Horsley, Shelton; Donaldson, Milton H.; Lovett, William L.; Brown, Peter W.; Ruffner, B. W.; Regelson, William

doi:10.1097/00000658-197505000-00016

Cited by 83 publications

(7 citation statements)

References 4 publications

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“…Moreover, the prognostic outcomes for patients with advanced CRC is poor [ 2 ]. 5-fluorouracil (5-Fu), which acts by interfering with cellular DNA synthesis and histone deacetylation, is recommended as a first-line chemotherapeutic option for CRC [ 3 , 4 ]. Clinically, administration of 5-Fu combined with irinotecan or oxaliplatin is considered to be a relatively standard chemotherapeutic regimen [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer

Zhang

Luo

Wang

et al. 2022

Aging

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5-Fluorouracil (5-Fu) is the first-line chemotherapeutic option for colorectal cancer. However, its efficacy is inhibited by drug resistance. Cytokines play an important role in tumor drug resistance, even though their mechanisms are largely unknown. Using a cytokine array, we established that tissue inhibitor metalloproteinase 2 (TIMP-2) is highly expressed in 5-Fu resistant colorectal cancer patients. Analysis of samples from 84 patients showed that elevated TIMP-2 expression levels in colorectal patients were correlated with poor prognostic outcomes. In a 5-Fu-resistant patient-derived xenograft (PDX) model, TIMP-2 was also found to be highly expressed. We established an autocrine mechanism through which elevated TIMP-2 protein levels sustained colorectal cancer cell resistance to 5-Fu by constitutively activating the ERK/MAPK signaling pathway. Inhibition of TIMP-2 using an anti-TIMP-2 antibody or ERK/MAPK inhibition by U0126 suppressed TIMP-2 mediated 5-Fu-resistance in CRC patients. In conclusion, a novel TIMP-2-ERK/MAPK mediated 5-Fu resistance mechanism is involved in colorectal cancer. Therefore, targeting TIMP-2 or ERK/MAPK may provide a new strategy to overcome 5-Fu resistance in colorectal cancer chemotherapy.

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Section: Introductionmentioning

confidence: 99%

TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer

Zhang

Luo

Wang

et al. 2022

Aging

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“…These strategies are multidirectional and composed of surgery, radiation therapy, chemotherapy, and targeted therapy (Damin & Lazzaron, 2014). Among them, chemotherapy utilizes different drugs or combinations of them and is administrated as an adjuvant after surgery (Goyle & Maraveyas, 2005; Lawrence et al 1978). Almost half of the CRC patients might develop recurrence due to surgical resection and aggressive chemotherapy, which underscore the necessity of improving novel therapies (de la Cueva et al, 2013; González‐Vallinas et al, 2013; Rangwala et al, 2012; P. R. Subbarayan et al, 2010; Wehler et al, 2013).…”

Section: Inhibition Of the Pi3k/akt/mtor Pathway In Crc Either As Mon...mentioning

confidence: 99%

The PI3K/Akt/mTOR axis in colorectal cancer: Oncogenic alterations, non‐coding RNAs, therapeutic opportunities, and the emerging role of nanoparticles

Sanaei

Khorasani

Pourbagheri‐Sigaroodi

et al. 2021

Journal Cellular Physiology

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Colorectal cancer (CRC) is one of the deadliest human malignancies worldwide. Several molecular pathways have been demonstrated to be involved in the initiation and development of CRC which among them, the overactivation of the phosphatidyl‐inositol 3‐kinase (PI3K)/Akt/mTOR axis is of importance. The current review aims to unravel the mechanisms by which the PI3K/Akt/mTOR pathway affects CRC progression; and also, to summarize the original data obtained from international research laboratories on the oncogenic alterations and polymorphisms affecting this pathway in CRC. Besides, we provide a special focus on the regulatory role of noncoding RNAs targeting the PI3K/Akt/mTOR pathway in this malignancy. Questions on how this axis is involved in the inhibition of apoptosis, in the induction of drug resistance, and the angiogenesis, epithelial to mesenchymal transition, and metastasis are also responded. We also discussed the PI3K/Akt pathway‐associated prognostic and predictive biomarkers in CRC. In addition, we provide a general overview of PI3K/Akt/mTOR pathway inhibition whether by chemical‐based drugs or by natural‐based medications in the context of CRC, either as monotherapy or in combination with other therapeutic agents; however, those treatments might have life‐threatening side effects and toxicities. To the best of our knowledge, the current review is one of the first ones highlighting the emerging roles of nanotechnology to overcome challenges related to CRC therapy in the hope that providing a promising platform for the treatment of CRC.

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“…Three trials have suggested that 5-fluorouracil is of value (Li & Ross 1976, Mackman et al 1974, Mavligit et al 1976, but all have relied on historical controls. The two studies showing no benefit (Grage et al 1975, Lawrence et al 1975 were, however, prospective randomized series. The value of 5-fluorouracil as an adjuvant in rectal cancer is doubtful, and it has been argued that the next step, which is already being taken in America, should be trials using a combination of drugs.…”

Section: Adjuvant Chemotherapymentioning

confidence: 99%

Recent Advances in Cytotoxic Therapy for Gastrointestinal Carcinoma: A Review

Priestman

1978

J R Soc Med

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Single-agent therapy Until recently the use of cytotoxic drug therapy in gastrointestinal cancer has been confined to the administration of single drugs to patients with advanced, incurable, disease. The results of this approach are summarized in Table I. The modest success of 5-fluorouracil, noted sooã fter its introduction 18 years ago, has tended to inhibit the evaluation of other agents, clinical resources being largely devoted to determining the optimum dose and route of administration for 5-fluorouracil. Mitomycin-C has been widely used in Japan, but there were fatalities with high doses when it was first used in the West. At lower doses it is a safe and valuable agent, but the stigma of the original toxicity has inhibited its acceptance. By the early 1970s it became clear that intermittent intravenous administration was the optimum regimen for 5-fluorouracil and nothing more could be expected from variations in the route of administration and dose schedules (Moertel 1975). Clinicians began to explore other drugs and this shift of attention corresponded with the appearance of several new compounds that were immediately assessed. This move directly from 5-fluorouracil to new agents has meant that many of the established anti-cancer drugs have been inadequately assessed in gastrointestinal cancer. The first group of new drugs to be screened were the nitrosoureas, comprising BCNU, CCNU and methyl-CCNU (Me-CCNU). The initial assessment suggested that MeCCNU and BCNU were active in stomach and large-bowel cancer. Subsequent comparative studies in large-bowel cancer showed that MeCCNU was more effective than BCNU and that, with an overall response rate of 26%, it might have an activity comparable to

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Chemotherapy as an Adjuvant to Surgery for Colorectal Cancer

Cited by 83 publications

References 4 publications

TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer

TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer

The PI3K/Akt/mTOR axis in colorectal cancer: Oncogenic alterations, non‐coding RNAs, therapeutic opportunities, and the emerging role of nanoparticles

Recent Advances in Cytotoxic Therapy for Gastrointestinal Carcinoma: A Review

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