The treatment algorithm of locally advanced rectal cancer has been changing in the last years and a multidisciplinary approach is required to select effective and personalized treatment. Nowadays, total neoadjuvant treatment is an established validated strategy for high-risk rectal cancer patients as it showed and has shown increased complete response rate representing a new standard of care. Therefore, the selection of predictive molecular markers is, even more, an essential and pursued medical needs goal. Moreover, regarding the early stage of disease, one major question pertains to the risk of recurrence and minimal residual disease: when is staging based on pathologic features adequate for a shared therapeutic decision? This is one of the main issues concerning future advances.
The role of liquid biopsy in rectal cancer as a minimally invasive and novel procedure could support either the diagnostic process or the evaluation of response to therapy treatment. The role of liquid biopsy in rectal cancer is being investigated as translational endpoint for obtaining tumour-derived components such as circulating tumour DNA (ctDNA), useful for risk stratification and detecting minimal residual disease. The presence of ctDNA has been strongly associated with adverse prognosis after curative treatment in localized disease. Moreover, it may represent a diagnostic alternative to tissue molecular testing.
The role function of the tumour microenvironment (TME) in supporting tumour development and progression is increasingly recognized as a critical feature of several tumours. The bed of tumours is characterized by adipocytes, tumour vasculature, lymphocytes, dendritic cells, and cancer-associated fibroblasts. Each of these cells has its own immunological capacity that affects the survival of cancer cells and interacts with neighbouring cells. The interaction between the stromal and cancer cells is a complex mechanism and contribute to editing the tumour microenvironment (TME). The TME is dynamic, following tissue restyling, metabolic alterations and changes in stromal cell recruitment that can be affected by both chemo-radiotherapy and immunotherapy. Studying cells in the TME during cancer treatment may explain response and resistance to therapy, help control neoplasms, and obtain new therapies.
Microsatellite instability (dMMR/MSI) is a recognized predictive marker of limited benefit from fluoropyrimidines therapy. As the backbone of systemic therapy, primary resistance to fluoropyrimidine raises concern, especially in locally advanced rectal cancer with the current shift of systemic treatment from the adjuvant to the neoadjuvant setting. Furthermore, a revolution in cancer therapy has been brewing. The efficacy of programmed cell death protein 1 (PD-1) blockade in microsatellite instability-high – defective mismatch repair (MSI -H-dMMR) cancers has been established and is the new standard of care for MSI-H tumours. Trials of immunotherapy in locally advanced dMMR rectal cancers are ongoing or being designed.
The focus of the proposed Research Topic is to underline:
• Advances in molecular biology knowledge of rectal cancer
• Development and forthcoming role of liquid biopsy
• TME: identification and characterization of immunological markers and their involvement in distinct cancer pathways
• Impact of MSI, opportunities and challenges of immunotherapy in rectal cancer
High-quality original research, review, and perspective articles highlighting the latest advancements in our knowledge of rectal cancer biology are welcome.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
The treatment algorithm of locally advanced rectal cancer has been changing in the last years and a multidisciplinary approach is required to select effective and personalized treatment. Nowadays, total neoadjuvant treatment is an established validated strategy for high-risk rectal cancer patients as it showed and has shown increased complete response rate representing a new standard of care. Therefore, the selection of predictive molecular markers is, even more, an essential and pursued medical needs goal. Moreover, regarding the early stage of disease, one major question pertains to the risk of recurrence and minimal residual disease: when is staging based on pathologic features adequate for a shared therapeutic decision? This is one of the main issues concerning future advances.
The role of liquid biopsy in rectal cancer as a minimally invasive and novel procedure could support either the diagnostic process or the evaluation of response to therapy treatment. The role of liquid biopsy in rectal cancer is being investigated as translational endpoint for obtaining tumour-derived components such as circulating tumour DNA (ctDNA), useful for risk stratification and detecting minimal residual disease. The presence of ctDNA has been strongly associated with adverse prognosis after curative treatment in localized disease. Moreover, it may represent a diagnostic alternative to tissue molecular testing.
The role function of the tumour microenvironment (TME) in supporting tumour development and progression is increasingly recognized as a critical feature of several tumours. The bed of tumours is characterized by adipocytes, tumour vasculature, lymphocytes, dendritic cells, and cancer-associated fibroblasts. Each of these cells has its own immunological capacity that affects the survival of cancer cells and interacts with neighbouring cells. The interaction between the stromal and cancer cells is a complex mechanism and contribute to editing the tumour microenvironment (TME). The TME is dynamic, following tissue restyling, metabolic alterations and changes in stromal cell recruitment that can be affected by both chemo-radiotherapy and immunotherapy. Studying cells in the TME during cancer treatment may explain response and resistance to therapy, help control neoplasms, and obtain new therapies.
Microsatellite instability (dMMR/MSI) is a recognized predictive marker of limited benefit from fluoropyrimidines therapy. As the backbone of systemic therapy, primary resistance to fluoropyrimidine raises concern, especially in locally advanced rectal cancer with the current shift of systemic treatment from the adjuvant to the neoadjuvant setting. Furthermore, a revolution in cancer therapy has been brewing. The efficacy of programmed cell death protein 1 (PD-1) blockade in microsatellite instability-high – defective mismatch repair (MSI -H-dMMR) cancers has been established and is the new standard of care for MSI-H tumours. Trials of immunotherapy in locally advanced dMMR rectal cancers are ongoing or being designed.
The focus of the proposed Research Topic is to underline:
• Advances in molecular biology knowledge of rectal cancer
• Development and forthcoming role of liquid biopsy
• TME: identification and characterization of immunological markers and their involvement in distinct cancer pathways
• Impact of MSI, opportunities and challenges of immunotherapy in rectal cancer
High-quality original research, review, and perspective articles highlighting the latest advancements in our knowledge of rectal cancer biology are welcome.
Please note: manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by validation (independent cohort or biological validation in vitro or in vivo) are out of scope for this section and will not be accepted as part of this Research Topic.
