Development of Novel Targeted Agents in the Treatment of Metastatic Colorectal Cancer

Berge, Eamon M.; Thompson, Chris; Messersmith, Wells A.

doi:10.1016/j.clcc.2011.06.011

Cited by 6 publications

(3 citation statements)

References 89 publications

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“…Few molecules destroy cancer cells without harming healthy tissues and the side effects of current cancer drugs are so common that they have become accepted as a necessary element of tumor therapy. Diverse technologies and conceptual approaches have therefore been explored to identify how tumor cells differ from healthy cells, to understand the mechanisms of tumorigenesis and to explore new targets for more tumor-selective therapies [3][4][5][6][7][8].…”

Section: Future Oncology Part Ofmentioning

confidence: 99%

“…A variety of approaches are being explored to identify new drugs that selectively kill tumor cells. Significant progress is being made and new, targeted therapies include inhibitors of growth factors and their receptors, blockers of angiogenesis and proapoptotic drugs [4][5][6]8]. A high degree of selectivity for tumor cells in vitro and in vivo has identified HAMLET as an interesting candidate drug with tumor specificity in animal models and clinical studies [13][14][15]75].…”

Section: In Vivo Effects Of Hamletmentioning

confidence: 99%

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HAMLET: Functional Properties and Therapeutic Potential

Rydström

Trulsson

et al. 2012

Future Oncol.

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Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity. The protein component of HAMLET is α-lactalbumin, which in its native state acts as a substrate specifier in the lactose synthase complex, thereby defining a function essential for the survival of lactating mammals. In addition, α-lactalbumin acquires tumoricidal activity after partial unfolding and binding to oleic acid. The lipid cofactor serves the dual role as a stabilizer of the altered fold of the protein and a coactivator of specific steps in tumor cell death. HAMLET is broadly tumoricidal, suggesting that the complex identifies conserved death pathways suitable for targeting by novel therapies. Sensitivity to HAMLET is defined by oncogene expression including Ras and c-Myc and by glycolytic enzymes. Cellular targets are located in the cytoplasmic membrane, cytoskeleton, mitochondria, proteasomes, lysosomes and nuclei, and specific signaling pathways are rapidly activated, first by interactions of HAMLET with the cell membrane and subsequently after HAMLET internalization. Therapeutic effects of HAMLET have been demonstrated in human skin papillomas and bladder cancers, and HAMLET limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue. These findings open up new avenues for cancer therapy and the understanding of conserved death responses in tumor cells.

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Section: Future Oncology Part Ofmentioning

confidence: 99%

Section: In Vivo Effects Of Hamletmentioning

confidence: 99%

HAMLET: Functional Properties and Therapeutic Potential

Rydström

Trulsson

et al. 2012

Future Oncol.

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“…CRC is a common malignant digestive tract tumor in China, which is characterized by the dissatisfactory therapeutic efficacy and poor prognosis ( 21 , 22 ). Chemotherapy plays an important role in the treatment of CRC, which, however, frequently fails and results in recurrence and metastasis due to the drug resistance of CRC cells ( 23 , 24 ).…”

Section: Discussionmentioning

confidence: 99%

Salidroside could enhance the cytotoxic effect of L‑OHP on colorectal cancer cells

et al. 2017

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Evidence has suggested that salidroside inhibits the proliferation and invasion of renal clear cell, lung, breast, and colon cancer. However, effect of salidroside on colorectal cancer (CRC) cells against oxaliplatin (L-OHP) resistance remains unclear. In the present study, the CRC HT-29 cell line and L-OHP resistance HT-29/L-OHP cell line were used to evaluate the effect, and mechanism of salidroside on L-OHP resistance. The results demonstrated that the activity of HT-29 cells was lower compared with that of HT-29/L-OHP cells following L-OHP intervention, and was accompanied with varied expression levels of drug resistant proteins. The combination of salidroside and L-OHP weakened cell activity significantly compared single utilization. Compared with the control group, salidroside intervention resulted in a higher percentage of HT-29/L-OHP cells in the G0/G1 stage, and reduced percentage in the G2/M stage, but no significant variation in the S stage. The HT-29/L-OHP cells exhibited increased apoptosis rates and caspase-3 activity, but decreased metastatic, and invasive abilities following salidroside intervention. Quantitative polymerase chain reaction and western blot analysis detected variations in the expression levels of associated genes in HT-29/L-OHP cells following salidroside intervention. In all, the results of the present study revealed that salidroside is able to decrease the activity and invasive capacity of HT-29/L-OHP cells, and treatment with salidroside is associated with increased apoptosis of cancer cells through the regulation of certain genes.

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