Introductory Chapter: Efforts to Conquer Colorectal Cancer from the Past to the Present

1. Introduction

In the United States, the incidence rate of colon cancer increased by 0.5% to 2.4% annually since the mid-1980s in adults aged 20 to 54 years. Moreover, the rectal cancer incidence rate also increased faster by 3.2% annually since the 1970s in relatively younger ages (20–29 years) [1]. The recent global trend of colorectal cancer has been reported to have confirmed about 1.14 million, which accounts for about 6% of all newly diagnosed cancer patients, and the annual mortality is approaching about 580 K [2]. Such facts make it possible to recognize the high incidence rate and mortality of colorectal cancer, and it gives a continuous challenge to conquer colorectal cancer for physicians and basic researchers. Up to now, a variety of treatments have been developed as strategies responding to metical unmet needs while succeeding with existing therapeutic options targeting colorectal cancer, and those options are still effective. Therefore, a broad understanding of recent therapies including the past things will be essential to lay the groundwork for the step-by-step process of making innovations in colorectal cancer treatment.

2. Conventional options for colorectal cancer treatment

The treatment of colon cancer is mainly well-known in three types: surgery, chemotherapy, and radiation therapy, and appropriate options are selected according to the stage of colorectal cancer between these therapies [3]. The progression of colorectal cancer is divided into stages from 0 to 4. Most cases of stage 0 colorectal cancer are forming as polyps that do not grow beyond the inner lining of the colon or rectum, the local lesions are excised through a colonoscopy or transanal resection [3, 4]. Stage 1 colorectal cancer has grown deeper into the layer of the colon or rectal wall, but it means that the cancer cells do not spread outside of the colon or rectal wall or into the nearby lymph nodes [3, 4]. Complete removal of polyps is done during the colonoscopy, and if cancer cells are not found at the edge of lesions after removal, no other treatment may be needed [3, 5]. Stage 2 means that the cancer cells have grown into nearby tissues outside the walls of the colon or rectum but have not spread to the lymph nodes [3, 4]. Treatment may require partial colectomy, which removes the portion of the colon or rectum that contains cancer along with the surrounding lymph nodes. If the risk of cancer recurrence is high, adjuvant chemotherapy may be recommended according to the status of microsatellite instability or mismatch repair gene expression [3, 5]. The main options for chemotherapy include a combination of 5-FU and leucovorin with oxaliplatin (FOLFOX) or capecitabine (XELOX), but other combinations are also available including radiation followed by surgery [6, 7, 8]. Stages 3 and 4 are belonging to advanced, refractory colorectal cancer, which means that spreads to nearby lymph nodes or distant organs (mainly the liver or lungs) [3, 4]. At these stages of colon cancer, surgery to remove the cancerous portion of the colon along with nearby lymph nodes followed by adjuvant chemotherapy is the standard treatment for this stage. For rectal cancer, FOLFOX, XELOX, or capecitabine alone is given along with radiation therapy followed by surgery to remove rectal cancer and nearby lymph nodes, usually by low anterior resection, proctectomy with coloanal anastomosis, or abdominoperineal resection [5, 6, 7]. If primary or spread colorectal cancer cannot be completely removed with surgery, treatment options are likely to be selected with chemo or targeted therapies, such as 5-FU, oxaliplatin, irinotecan, capecitabine, bevacizumab, cetuximab, and/or regorafenib used alone or in combination [3, 6, 7]. A relatively wide range of treatment options depending on the stage of colorectal cancer may give hope to the patients for a cure, and providing a variety of options to physicians can also have important implications in terms of effective cancer management in clinical. However, it should not be overlooked that even in the presence of these known options, colorectal cancer has not yet been conquered. This is because even if these standard options are applied, there are still limitations in treatment. Briefly, recurrence after surgery, resistance to chemotherapies by mutations, and side effects of radiation therapy have been considered the main difficulties, therefore attempts to find bettered therapeutics to overcome these limitations are undergoing.

3. Finding better therapeutics

The recently developed robotic resection offers the clinical advantage of a more precise incision than laparoscopy in the narrow space where the rectum is located and these precision technologies are constantly being improved [9]. The development of immunotherapeutic agents such as programmed death-ligand 1 antibodies, therapeutic chimeric antigen receptor-T cells, and cancer vaccines is also believed to be a remarkable achievement in taking one step closer to conquering colorectal cancer [10]. In addition, the development of sotorasib also means a breakthrough in the treatment of intractable cancer by mutation, recent clinical trials reported a disease control rate of about 73.8% targeting KRAS^G12C expressed colorectal cancer [11]. The case opens up the possibility that RAS mutations may no longer be defined as an area of an incurable disease. Along with these latest endeavors for the development of suitable therapies, several conditions that must be considered in order to develop better innovative therapies in the future or to overcome the limitations for the increase in therapeutic efficiency can be considered as follows: 1. Innovative diagnostic technologies such as proteomics, organoid culture, and virtual colonoscopy are encouraged to be included preferentially, and a developmental strategy reflecting characteristics of the target (eg. cancer stage, genetic predisposition, immune surveillance, and so on) is required. 2. Characteristics of the surrounding and internal microenvironment of the tumor, such as cancer-specific metabolism governing biochemical reaction by sphingolipids, characteristics of the tumor immune microenvironment, and the activity of microorganisms in the tumor, should be taken into account. 3. It would be important to select essential nutrients in consideration of the patient’s health condition and to find a strategy that can optimize their supply or control methods. Of course, these three categories for better colorectal cancer treatment are handled in this book with interest.

4. Closing remarks

Strategies for targeting colorectal cancer based on existing treatments are gradually being developed, but they do not overcome the recognized limitations yet. Therefore, based on an understanding of various treatment methods from the past to the present, better and more innovative treatments should be proposed with the optimal diagnostic condition, cancer stage, tumor microenvironment, and nutrition should be considered. I hope that readers will be able to shape their ideas for the future of colorectal cancer treatment based on the content of this book.

Conflict of interest

No conflict of interest exists with the publication of this chapter.