Personalized Identification of Optimal HIPEC Perfusion Protocol in Patient-Derived Tumor Organoid Platform

Organoids were first established as a three-dimensional cell culture system from mouse small intestine. Subsequent development has made organoids a key system to study many human physiological and pathological processes that affect a variety of tissues and organs. In particular, organoids are becoming very useful tools to dissect colorectal cancer (CRC) by allowing the circumvention of classical problems and limitations, such as the impossibility of long-term culture of normal intestinal epithelial cells and the lack of good animal models for CRC. In this review, we describe the features and current knowledge of intestinal organoids and how they are largely contributing to our better understanding of intestinal cell biology and CRC genetics. Moreover, recent data show that organoids are appropriate systems for antitumoral drug testing and for the personalized treatment of CRC patients.

Section: Organoids As a Platform For Screening Assaysmentioning

confidence: 99%

Organoids and Colorectal Cancer

Barbáchano

Fernández‐Barral

Bustamante-Madrid

et al. 2021

“…This was recently investigated using patient-derived organoids from colorectal cancer PM. In this study by Forsythe, low dose heated oxaliplatin (200 mg/m 2 ) for 200 min appeared to be more effective in terms of cytotoxicity than a higher dose of oxaliplatin (460 mg/m 2 ) for only 30 min [36].…”

Section: Use Of Hyperthermiamentioning

confidence: 73%

“…However, oxaliplatin as a HIPEC agent failed in recent randomized trials in colorectal cancer. Possibly, additional factors such as choice of carrier solution, target temperature, and treatment duration are important determinants of the efficacy of oxaliplatin, as recently demonstrated in organoid models [36,52].…”

Section: Choice and Combination Of Chemotherapymentioning

confidence: 99%

Hyperthermic Intraperitoneal Chemotherapy: A Critical Review

Ceelen

Demuytere

Hingh

2021

With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal. As a result, the true value of HIPEC in the treatment of peritoneal metastases remains a matter of debate. The current review aims to provide a critical overview of the theoretical concept and preclinical and clinical study results, to outline areas of persisting uncertainty, and to propose a framework to better define the role of HIPEC in the treatment of peritoneal malignancies.

“…Kim et al do note that feasibility concerns may pose an obstacle to more mainstream incorporation of organoid technology in cases of rare genetic alterations; however, they also recognize the benefits of organoids in identifying potential gene-drug interactions; examples include an association between RNF43 mutant tumors and Wnt inhibitors [ 139 , 143 ]. Recent studies of colon and appendiceal cancers have demonstrated that organoids can be successfully established in up to 75% of cases and that organoid response to administered chemotherapeutic treatment is similar to that of response in parent tissue [ 144 , 145 ]. The feasibility of such studies offers hope for future applications of tumor organoids in a bid to drive clinical decision-making on an individualized basis.…”

Section: Platforms For Personalized Approachmentioning

confidence: 99%

Precision Approaches in the Management of Colorectal Cancer: Current Evidence and Latest Advancements towards Individualizing the Treatment

Shuford

Cairns

Moaven

2020

Self Cite

The genetic and molecular underpinnings of metastatic colorectal cancer have been studied for decades, and the applicability of these findings in clinical decision making continues to evolve. Advancements in translating molecular studies have provided a basis for tailoring chemotherapeutic regimens in metastatic colorectal cancer (mCRC) treatment, which have informed multiple practice guidelines. Various genetic and molecular pathways have been identified as clinically significant in the pathogenesis of metastatic colorectal cancer. These include rat sarcoma (RAS), epithelial growth factor receptor (EGFR), vascular endothelial growth factor VEGF, microsatellite instability, mismatch repair, and v-raf murine sarcoma viral oncogene homolog b1 (BRAF) with established clinical implications. RAS mutations and deficiencies in the mismatch repair pathway guide decisions regarding the administration of anti-EGFR-based therapies and immunotherapy, respectively. Furthermore, there are several emerging pathways and therapeutic modalities that have not entered mainstream use in mCRC treatment and are ripe for further investigation. The well-established data in the arena of targeted therapies provide evidence-based support for the use or avoidance of various therapeutic regimens in mCRC treatment, while the emerging pathways and platforms offer a glimpse into the future of transforming a precision approach into a personalized treatment.