Stem Cell Therapy in Colorectal Cancer - An Overview

Introduction

Cancer stem cells are an excellent therapeutic candidate for colorectal cancer but are challenging to analyze due to the complexity of their isolation. The therapy alternatives available for colorectal cancer have improved over the years and have enhanced the total survival of colorectal cancer patients.

Nevertheless, the reaction rate for colorectal cancer patients with metastatic disease stays low and reduces by following the lines of treatment. The clinical management of cases with metastatic colorectal cancer (mCRC) delivers a unique challenge in balancing the advantages and disadvantages while taking into consideration disease progression, therapy-associated toxicities, drug resistance, and the patient's total quality of life.

Despite the initial success of treatment, the evolution of drug resistance can direct treatment failure and relapse in cancer cases, which can be attributed to cancer stem cells. Thus, colorectal cancer stem cells help with treatment resistance and the initiation of tumor and metastasis development, making them attractive potential candidates for managing colorectal cancer.

Novel therapeutic approaches are required to destroy tumor growth and metastasis while considering the tumor microenvironment, which plays an essential role in tumor cell plasticity.

What Has Been Known About the Origin of Colorectal Cancer Stem Cell?

The history of cancer stem cells goes back two decades ago with the finding of cancer stem cells in human acute myeloid leukemia. For the first time, a cell competent in initiating human acute myeloid leukemia in immunodeficient mice and having differentiation, proliferation, and self-renewal abilities were explained.

After some years, utilizing comparable experimental methods, cancer stem cells were found to exist in solid cancers like colorectal cancer. The origin of cancer stem cells in colorectal cancer is controversial, and multiple hypotheses were suggested. Colorectal cancer stem cells are connected with the acquisition of malignant molecular and cellular changes either due to the number of genetic and epigenetic modifications in restricted stem cells or progenitor cells and normal tumor cells or to the dedifferentiation of somatic cells induced by diverse genetic factors and environmental factors.

Colorectal cancer stem cells show tumor-related factors like uncontrolled growth, tumorigenicity, and treatment resistance. They may include a small reservoir of drug-resistant cells accountable for relapses following chemotherapy-induced remission, comprehended as minimal residual disease and distant metastasis. Therefore, colorectal cancer stem cells play a critical role in the initiation, invasion, and progression of colon rectal cancer and resistance to treatment.

These colorectal cancer stem cells improve heterogeneous tumors that can be serially transplanted into immunodeficient mice that compare to the original tumor. In addition, colorectal cancer stem cells can develop disseminated metastatic tumors due to their vast proliferative potential. One of the primary difficulties in studying colorectal cancer stem cells is their isolation due to their lower percentage within the tumor.

Nevertheless, the colorectal cancer stem cell population seems to be phenotypically and functionally heterogeneous and active, which is another obstacle to their isolation. Thus, developing treatments that selectively eliminate colorectal cancer stem cells present good opportunities for a tolerable clinical reaction but needs adequate technologies to find and isolate them.

Explain the Clinical Relevance of Colorectal Cancer Stem Cells.

Therapeutic advancements in recent decades have enabled most cancer patients to provide significant clinical responses. Nevertheless, although therapeutic procedures are advancing, none of these therapy modalities is curative in most cases of advanced colon rectal cancer. Similarly, despite initial successful therapy, on image studies of the therapeutic impact on the cells that create the tumor bulk, it has been found that tumor recurrence is nearly unavoidable due to the effect of drug resistance attributed to colorectal cancer stem cells.

Clinical Management of Colorectal Cancer

• Therapy choices and suggestions rely on numerous factors involving the patient's general health, potential side effects, the kind and stage of the tumor, and the mutational status and mutation and mismatch repair status. Treatment procedures for treating colorectal cancer are surgical resection, local treatments for metastatic disease, systemic therapy including chemotherapy, targeted treatment and immunotherapy, and palliative chemotherapy. Personalized treatment is necessary to allow cancer patients to increase the advantages while reducing the disadvantages to provide an optimal survival rate and improve these patients' quality of life.
• Surgical removal is the mainstay of corrective-purpose therapy for localized and advanced colorectal cancers. Still, it needs to be evaluated entirely when there is a regional invasion or histological characteristics with a poor prognosis. Surgical procedures can be connected with neoadjuvant treatment to shrink tumor mass and promote medical operation and with adjuvant treatment to restrict cancer recurrence. Significantly, neoadjuvant chemotherapy, possibly coupled with radiotherapy, is specifically suggested for rectal cancers. Therapy regimens for patients with localized colon-rectal cancers typically are chemotherapy, such as 5-fluorouracil (5-FU) alone or in combination. Leucovorin (folinic acid) is generally administered with 5-FU to improve its anti-tumor effect. Despite numerous advances in colon-rectal cancer therapy, around 20 % of new colon-rectal cancer cases are already metastatic. The most typical sites of metastatic colorectal cancer are the liver, lungs, and peritoneum. Unfortunately, up to 50 percent of patients with an early-stage diagnosis will ultimately produce metastatic disease, and 80 % to 90 % have the unresectable metastatic disease due to its size, site, and extent of disease.

• The selection of local treatments depends on the site and the extent of the metastases. Local therapies are endorsed for metastatic colorectal cancer with inoperable lesions. For cases with unresectable liver or lung metastases, radiofrequency ablation is suggested for treating small lesions and medium-sized lesions. Still, for more extensive lesions and those close to vascular structures, microwave ablation or stereotactic body radiation treatment may be good options.

• Local treatments can be issued with curative or palliative intent and are most often utilized with systemic therapy. Liver metastases can also be managed by a higher dosage of chemotherapy instantly into the hepatic artery corresponding to systemic therapy, that is, hepatic arterial infusion or by combining drug administration or radiation administration with blood vessel obstruction. For cases with peritoneal metastases, cytoreductive surgical procedures and hyperthermic intraperitoneal chemotherapy are suggested.

• Systemic treatment for colorectal cancer seeks to reduce the primary tumor or metastases to transform them to a resectable size and improve progression-free survival. Cases with advanced colorectal cancer typically have several lines of treatment, most often involving a combination of chemotherapy with targeted treatment or immunotherapy, based on tumor mutational and mutation and mismatch repair status.

Conclusion:

Targeting colorectal cancer stem cells provides a guarantee for preventing relapse and metastasis in colon-rectal cancer patients. In addition, due to the primary reason for drug resistance, colorectal cancer stem cells are potential targets for treating colorectal cancer. Nevertheless, the effect of therapeutic agents, mainly targeting colorectal cancer stem cells, is complex. Despite the rising number of treatments, resistance mechanisms may arise and thus complicate the therapeutic management of patients with colorectal cancer.