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Updates on Clinical Trials in Diagnosis and Therapy of Colorectal Cancer

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Colon Cancer Diagnosis and Therapy Vol. 3

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Abstract

Colorectal cancer (CRC) is the third most common cancer overall. CRC could be sporadic, which is most common at 70% of CRC, inherited (5%), and familial (25%). The most common genes that are affected in CRC are oncogenes, tumor suppressor genes, and genes related to the DNA repair mechanisms. Structural screening tests (such as colonoscopy, sigmoidoscopy) are superior to stool tests. Studies have shown that colonoscopy has reduced the incidence of CRC by 67% and case fatality rate by 65%. Microsatellite instability (MSI), chromosomal instability (CIN), and CpG island methylator phenotype (CIMP) are the major mutations that occur in CRC. These can also act as biomarker, which could be detected in stool, blood, or tumor biopsy. Based on patient characteristics and tumor features, CRC patients could be divided into four groups (from Group 0 to Group 3). First-line chemotherapeutic agents for adjuvant chemotherapy are FOLFOX (5-FU/LV/Oxaliplatin) or capecitabine/LV/oxaliplatin. Palliative chemotherapy options involve 5-FU with leucovorin, capecitabine alone, FOLFOX or FOLFIRI regiments (5-FU/LV/irinotecan). Efficacy of combination regimens are enhanced by the use of monoclonal antibodies such as anti-VEGF (bevacizumab) and anti-EGFR (cetuximab, panitumumab). Some of the alternative treatments currently ongoing are discussed in this chapter. These include agarose tumor microbeads where tumor growth inhibitory factor causing a negative inhibitory signal is found to slow the tumor growth. Chronic inflammatory products such as cytokines, chemokines, reactive oxygen species (ROS), reactive nitrogen species, and arachidonic acid derivatives are risk factors for CRC, and COX inhibitors such as NSAIDs could have some effect prophylactically and for treatment against CRC. Probiotics could act on CRC possibly by apoptosis of diseased cells and also possibly by antioxidant effect. Functional foods containing polyphenols could reduce ROS, thereby reducing CRC by maintaining a balance between ROS and antioxidants. Metal-based drugs such as platinum-based agents (like carboplatin, oxaliplatin) and gold-based drugs (such as auranofin) also exerts antitumor effect, possibly through platinum-DNA adducts and ROS, respectively.

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Abbreviations

BMI:

Body mass index

CAPOX:

Capecitabine/LV/oxaliplatin

CIMP:

CpG island methylator phenotype

CIN:

Chromosomal instability

COX:

Cyclooxygenase

COXibs:

Cyclooxygenase-2 inhibitor

CRC:

Colorectal carcinoma

CT:

Computerized tomography

CVD:

Cardiovascular disease

DNA:

Deoxyribonucleic acid

EGFR:

Epidermal growth factor receptor

FAP:

Familial adenomatous polyposis

FBLN1:

Fibulin

FOLFIRI:

5-FU/LV/irinotecan

FOLFOX:

5-FU/LV/oxaliplatin

GLOBOCAN:

Global Cancer Observatory

GSN:

Gelsolin

KRAS:

Kirsten rat sarcoma viral oncogene homolog

MSI:

Microsatellite instability

NCL:

Nucleolin

NSAIDs:

Non-steroidal anti-inflammatory drugs

PEBP1:

Phosphatidylethanolamine-binding protein

PEDF:

Pigment epithelium-derived factor

PRDX1:

Peroxiredoxin-1

PSAP:

Prosaposin

RENCA:

Renal cortical adenocarcinoma cell line (mouse)

RNA:

Ribonucleic acid

RON:

Reactive nitrogen species

ROS:

Reactive oxygen species

Serbp1:

Serpine1

SPARC:

Secreted protein, acidic, and rich in cysteine

TIMP2:

Tissue inhibitor of metalloproteinase 2

USPSTF:

United States Preventive Services Task Force

VEGF:

Vascular endothelial growth factor

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Acknowledgments

The authors are grateful to Ms. Kristina K. Greiner for graphics assistance.

Conflict of Interest Disclosure

The authors have no conflicts of interest with this research work.

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Authors and Affiliations

  1. Department of Internal Medicine, Khyber Teaching Hospital, Peshawar, Khyber Pakhtunkhwa, Pakistan

    Farhan Ullah, Maha Wazir & Sana Hussain

  2. Department of Internal Medicine, University of Iowa, Iowa City, IA, USA

    Hariharasudan Mani & Saeed Ali

  3. AdventHealth Cancer Institute, FSU and UCF Colleges of Medicine, Orlando, FL, USA

    Sarfraz Ahmad

Authors
  1. Farhan Ullah
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  2. Hariharasudan Mani
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  3. Maha Wazir
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  4. Sana Hussain
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  5. Saeed Ali
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  6. Sarfraz Ahmad
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Correspondence to Sarfraz Ahmad .

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Editors and Affiliations

  1. Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India

    Dhananjay Shukla

  2. Department of Biotechnology, Guru Ghasidas Vishwavidyalaya, Bilaspur, Chhattisgarh, India

    Naveen Kumar Vishvakarma

  3. Division of Hematology and Oncology, School of Medicine, University of Alabama, Birmingham, AL, USA

    Ganji Purnachandra Nagaraju

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Ullah, F., Mani, H., Wazir, M., Hussain, S., Ali, S., Ahmad, S. (2022). Updates on Clinical Trials in Diagnosis and Therapy of Colorectal Cancer. In: Shukla, D., Vishvakarma, N.K., Nagaraju, G.P. (eds) Colon Cancer Diagnosis and Therapy Vol. 3. Springer, Cham. https://doi.org/10.1007/978-3-030-72702-4_1

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