Colorectal cancer: Genetic alterations, novel biomarkers, current therapeutic strategies and clinical trials

Abstract

Colorectal cancer (CRC) is the third most commonly detected cancer with a serious global health issue. The rates for incidence and mortality for CRC are alarming, especially since the prognosis is abysmal when the CRC is diagnosed at an advanced or metastatic stage. Both type of (modifiable/ non-modifiable) types of risk factors are established for CRC. Despite the advances in recent technology and sophisticated research, the survival rate is still meager due to delays in diagnosis. Therefore, there is urgently required to identify critical biomarkers aiming at early diagnosis and improving effective therapeutic strategies. Additionally, a complete understanding of the dysregulated pathways like PI3K/Akt, Notch, and Wnt associated with CRC progression and metastasis is very beneficial in designing a therapeutic regimen. This review article focused on the dysregulated signaling pathways, genetics and epigenetics alterations, and crucial biomarkers of CRC. This review also provided the list of clinical trials targeting signaling cascades and therapies involving small molecules. This review discusses up-to-date information on novel diagnostic and therapeutic strategies alongside specific clinical trials.

Keywords: Biomarkers; Colorectal cancer; Epigenetics; Small molecules; Targeted pathways.

Fig. 1.

Risk factors for colorectal cancer (CRC).

Figure 2.. Activation of VEGR and EGFR activation impacts CRC cell growth.

The intracellular tyrosine kinase domain activates pro-angiogenic intracellular processes via PLC, PKC, and NOS proteins leading to angiogenesis. Activation of EGFR initiates RAS/RAF/MEK and PI3K/AKT signaling cascades, and promoting cell proliferation and survival, respectively.