Emerging Treatments For Colorectal Cancer

  • Zahra Khan MSc Neuroscience, University of Toronto
  • Yuna Chow BSc (Hons), Medicine, University of St Andrews

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Overview

Being often considered a "second brain" by experts in the field, the gut is an organ with important functions that regulate not only digestion but also the production of hormones that impact the way we feel and behave. Therefore diseases that disrupt its normal function are often the focus of research. 

Colorectal cancer is among the most frequent types of cancer, and it is located in the final part of the human gut. Although the word "cancer" often provokes emotions of anxiety and fear, today there is hope on the horizon. New emerging treatments, in combination with traditional options, and earlier diagnosis, have significantly improved the survival and quality of life of people living with the disease.  

Introduction

Definition of colorectal cancer

Colorectal cancer is a type of cancer affecting the large intestine of the digestive system, specifically the last part, which is the colon or rectum. According to global statistics calculated by the Agency for Research on Cancer (IARC), colorectal cancer is a threatening disease – in 2022 it was the third most commonly diagnosed cancer and the second leading cause of cancer-related death with a percentage of 9.3% among all types.1 

Staging of the tumours at the time of diagnosis is important for the decision of the appropriate treatment. Later stages with metastatic disease, indicating that cancer has spread to other organs, are harder to control and manage. 

Colorectal cancer has been linked to both genetic and environmental factors. A Westernised diet characterised by processed meat, alcohol, and low consumption of fruit and vegetables in combination with a sedentary lifestyle increases the risk of developing colorectal cancer.2 

Importance of emerging treatments

Prevention can be life-saving, as removal of precancerous or early-stage lesions in the colon or rectum is determining for the survival of patients. Implemented screening programs and improved management have contributed to the reduction of overall numbers of incidence and mortality, however, the numbers remain high.3 In addition, in recent years cases of young-onset colorectal cancer have increased, a fact that is often attributed to lifestyle choices.4 Therefore, it is of foremost importance to develop new effective treatments that will in combination with conventional therapies improve the outcome for patients.

Traditional treatments for colorectal cancer

Traditional treatments describe conventional therapeutic strategies that have been used for years against colorectal cancer. These include surgical resection of the tumour, followed by chemotherapy or radiotherapy.5 Although these therapies are beneficial, especially for early stage patients, they are not effective for advanced stages. Moreover, multidrug resistance often occurs after a while, creating an urgent need for new approaches.6

Emerging treatments

Immunotherapy

Immunotherapy is a treatment that boosts the immune system of the patient to fight cancer. Immunotherapeutic medications allow components of the immune system of the host to target and eliminate tumour cells.7 This can be achieved through the administration of reagents that allow the activation of immune cells, through genetic engineering of immune cells, or through vaccines that boost the immune response. In recent years clinical trials have shown it is successful in a variety of cancers, including some types of colorectal cancer. 

Immunotherapy has been effective and approved as first- or second-line treatment in a subset of colorectal cancer patients displaying a high mutagenic status (genetic mutation). Namely, Pembrolizumab and Nivolumab are inhibitors of Programmed Cell Death 1 (PD-1), an important protein of immune inactivation. In 2018, Ipilimumab, an inhibitor of a receptor that decreases immune response, was approved for a combination treatment with Nivolumab. 8

Targeted therapy

Targeted therapy in cancer targets specific components in tumour cells that contribute to the rapid growth or spreading capacity of those cells. It usually includes small molecules or antibodies that aim and interact with proteins of the cancerous cells. In this way, these proteins can be blocked, limiting the growth of the cells. In other examples, the antibodies target features of the cells and mark them so they are more recognisable by immune cells for elimination.

In colorectal cancer, several targeted therapies are already used in clinical practice, according to the specific characteristics found in the tumours of each individual. Several proteins of the tumour cells regulating their growth and survival can be aimed with the administration of these monoclonal antibodies. These include: 

  • Cetuximab or Panitumumab to target Epidermal Growth Factor Receptor (EGFR) 
  • Regorafenib or Ramucirumab to target Vascular Endothelial Growth Factor (VEGF)   
  • Trastuzumab or Pertuzumab to target Human Epidermal Growth Factor Receptor (HER-2)
  • Dabrafenib and Trametinib to target other proteins (BRAF-MEK).9   

Precision medicine

The term precision medicine describes therapeutic approaches that are adapted to the specific needs of individuals. Unique features of the patients are initially examined and then a treatment plan is designed. In this way, therapeutic schemes can be more effective and beneficial.

Colorectal cancer is highly heterogeneous among different cases, and therefore there is not a therapeutic protocol fitting all patients. A biopsy of the tumour contributes to the characterization of its molecular and histological features. This in combination with additional information regarding the exact location of the tumour or other clinical features is considered by clinicians prior to designing the most fitting scheme. 

Consequences from various cancer treatments often have serious adverse effects that are harmful to the human body, a fact that underlines further the importance of more suitable treatments. It is also worth mentioning that in precision medicine all previously mentioned options are considered, including surgery, radiation, chemotherapies, immunotherapies, and targeted therapies. The goal of this evolving field is to proceed with the most beneficial option or combination of options based on a detailed characterization of tumours.10

Clinical trials

Several clinical trials are currently ongoing for colorectal cancer. Clinicians and researchers cooperate to establish new effective solutions to battle this disease. Different aspects are currently investigated regarding dosing, combinations of drugs, vaccines, and nutrition among others. Additionally, clinical trials test the safety and adverse effects of new drugs. They need a large number of patients and are time-consuming, but they are necessary for the approval of a new therapeutic protocol. The list of ongoing clinical trials for colorectal cancer can be found in various sources.  

Challenges and future directions

Despite the important progress in oncology, several challenges remain for the successful treatment of all cases of colorectal cancer. Unfortunately, several patients do not respond to the currently available treatments, and therefore detailed screening and classification of the disease is necessary. Another challenge is multidrug resistance, an obstacle that can be overcome by the discovery of additional vulnerabilities of the tumours. As a result, research is a priority for the implementation and evolution of precision medicine in colorectal cancer.11, 12 

Summary

Emerging treatments have revolutionised the field of oncology in recent years. For colorectal cancer immunotherapy and targeted therapy in combination with conventional therapies have significantly improved the life expectancy of patients. These treatments are brought under the scope of precision medicine, a promising field that adjusts therapeutic schemes according to the personal needs of each individual. Further research creates the possibility of an inclusion of all cases and the development of effective lasting therapies for colorectal cancer. 

FQ&A

How high was the increase in colorectal cancer incidents in recent years among young individuals?

Among younger individuals, aged less than 55 years old, the percentage of colorectal cancer incidence increased to 20% in 2019, in comparison to the percentage of 11% in 2011.13

How much was the reduction of the mortality rate of colorectal cancer in recent years?

The mortality rate among individuals with colorectal cancer overall decreased by 2% annually between 2011-2020.13

What lifestyle adaptations can reduce the probability of colorectal cancer occurrence?

Several lifestyle choices can decrease the risk of colorectal cancer. These include:

  • A diet rich in fruit, vegetables, fibre and omega-3 fatty acids
  • Increased physical activity
  • Decreased consumption of processed and red meat
  • Decreased consumption of alcohol
  • Smoking Cessation

Some studies have indicated that vitamin D and dairy consumption might also be beneficial, but this remains to be further validated.14

Is the administration of probiotics beneficial as a complementary therapy for colorectal cancer?

Several studies have indicated that probiotics contribute to the prevention of colorectal cancer and increase the effectiveness of therapy. However, these studies need further validation. It is important to always consult a specialist doctor before receiving any supplements.15

References

  1. Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin [Internet]. 2024;74(3):229–63. Available from: https://pubmed.ncbi.nlm.nih.gov/38572751/
  2. Ionescu VA, Gheorghe G, Bacalbasa N, Chiotoroiu AL, Diaconu C. Colorectal cancer: from risk factors to oncogenesis. Medicina (Kaunas) [Internet]. 2023 Sep 12;59(9):1646. Available from: https://pubmed.ncbi.nlm.nih.gov/37763765/
  3. Senore C, Lansdorp-Vogelaar I, de Jonge L, Rabeneck L. Rationale for organised Colorectal cancer screening programs. Best Pract Res Clin Gastroenterol [Internet]. 2023 Oct;66:101850. Available from: https://pubmed.ncbi.nlm.nih.gov/37852709/
  4. Spaander MCW, Zauber AG, Syngal S, Blaser MJ, Sung JJ, You YN, et al. Young-onset colorectal cancer. Nat Rev Dis Primers [Internet]. 2023 Apr 27;9(1):21. Available from: https://pubmed.ncbi.nlm.nih.gov/37105987/
  5. Dariya B, Aliya S, Merchant N, Alam A, Nagaraju GP. Colorectal cancer biology, diagnosis, and therapeutic approaches. Crit Rev Oncog [Internet]. 2020;25(2):71–94. Available from: https://pubmed.ncbi.nlm.nih.gov/33389859/
  6. Van der Jeught K, Xu HC, Li YJ, Lu XB, Ji G. Drug resistance and new therapies in colorectal cancer. World J Gastroenterol [Internet]. 2018 Sep 14;24(34):3834–48. Available from: https://pubmed.ncbi.nlm.nih.gov/30228778/
  7. Abbott M, Ustoyev Y. Cancer and the immune system: the history and background of immunotherapy. Semin Oncol Nurs [Internet]. 2019 Oct;35(5):150923. Available from: https://pubmed.ncbi.nlm.nih.gov/31526550/
  8. Al Zein M, Boukhdoud M, Shammaa H, Mouslem H, El Ayoubi LM, Iratni R, et al. Immunotherapy and immunoevasion of colorectal cancer. Drug Discov Today [Internet]. 2023 Sep;28(9):103669. Available from: https://pubmed.ncbi.nlm.nih.gov/37328052/
  9. Manzi J, Hoff CO, Ferreira R, Pimentel A, Datta J, Livingstone AS, et al. Targeted therapies in colorectal cancer: recent advances in biomarkers, landmark trials, and future perspectives. Cancers (Basel) [Internet]. 2023 Jun 1 [cited 2024 Jun 13];15(11):3023. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252368/
  10. Riedesser JE, Ebert MP, Betge J. Precision medicine for metastatic colorectal cancer in clinical practice. Ther Adv Med Oncol [Internet]. 2022;14:17588359211072703. Available from: https://pubmed.ncbi.nlm.nih.gov/35237350/
  11. Ciardiello F, Ciardiello D, Martini G, Napolitano S, Tabernero J, Cervantes A. Clinical management of metastatic colorectal cancer in the era of precision medicine. CA Cancer J Clin [Internet]. 2022 Jul;72(4):372–401. Available from: https://pubmed.ncbi.nlm.nih.gov/35472088/
  12. Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, Shia J, Segal NH, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol [Internet]. 2019 Jun;16(6):361–75. Available from: https://pubmed.ncbi.nlm.nih.gov/30886395/
  13. Siegel RL, Wagle NS, Cercek A, Smith RA, Jemal A. Colorectal cancer statistics, 2023. CA Cancer J Clin [Internet]. 2023;73(3):233–54. Available from: https://pubmed.ncbi.nlm.nih.gov/36856579/
  14. Song M, Chan AT. Environmental factors, gut microbiota, and colorectal cancer prevention. Clin Gastroenterol Hepatol [Internet]. 2019 Jan;17(2):275–89. Available from: https://pubmed.ncbi.nlm.nih.gov/30031175/
  15. Eslami M, Yousefi B, Kokhaei P, Hemati M, Nejad ZR, Arabkari V, et al. Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol [Internet]. 2019 Aug;234(10):17127–43. Available from: https://pubmed.ncbi.nlm.nih.gov/30912128/

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.
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