Colorectal cancer (CRC) is the third most frequently detected type of cancer, and the second most common cause of cancer‑related mortality globally. The American Cancer Society predicted that approximately 147,950 individuals would be diagnosed with CRC, out of which 53,200 individuals would succumb to the disease in the USA alone in 2020. CRC‑related mortality ranks third among both males and females in the USA. CRC arises from 3 major pathways: i) The adenoma‑carcinoma sequence; ii) serrated pathway; and iii) the inflammatory pathway. The majority of cases of CRC are sporadic and result from risk factors, such as a sedentary lifestyle, obesity, processed diets, alcohol consumption and smoking. CRC is also a common preventable cancer. With widespread CRC screening, the incidence and mortality from CRC have decreased in developed countries. However, over the past few decades, CRC cases and mortality have been on the rise in young adults (age, <50 years). In addition, CRC cases are increasing in developing countries with a low gross domestic product (GDP) due to lifestyle changes. CRC is an etiologically heterogeneous disease classified by tumor location and alterations in global gene expression. Accumulating genetic and epigenetic perturbations and aberrations over time in tumor suppressor genes, oncogenes and DNA mismatch repair genes could be a precursor to the onset of colorectal cancer. CRC can be divided as sporadic, familial, and inherited depending on the origin of the mutation. Germline mutations in APC and MLH1 have been proven to play an etiological role, resulting in the predisposition of individuals to CRC. Genetic alterations cause the dysregulation of signaling pathways leading to drug resistance, the inhibition of apoptosis and the induction of proliferation, invasion and migration, resulting in CRC development and metastasis. Timely detection and effective precision therapies based on the present knowledge of CRC is essential for successful treatment and patient survival. The present review presents the CRC incidence, risk factors, dysregulated signaling pathways and targeted therapies.

Colorectal cancer (CRC) is the second most common malignancy causing cancer‑related mortality globally. It is the third most common type of cancer detected worldwide. The recent concept of the human body supporting a diverse community of microbes has revealed the important role these microbes play synergistically in maintaining normal homeostasis. The balance between the microbiomes and epithelial cells of the human body is essential for normal physiology. Evidence from meta‑genome analysis indicates that an imbalance in the microbiome is prominent in the guts of patients with CRC. Several studies have suggested that the gut microbiota can secrete metabolites [short‑chain fatty acids (SCFAs), vitamins, polyphenols and polyamines] that modulate the susceptibility of the colon and rectum by altering inflammation and DNA damage. The state of microbiome imbalance (dysbiosis) has been reported in patients with CRC, with an increasing population of ‘bad’ microbes and a decrease in ‘good’ microbes. The ‘good’ microbes, also known as commensal microbes, produce butyrate; however, ‘bad’ microbes cause a pro‑inflammatory state. The complex association between pathological microbial communities leading to cancer progression is not yet fully understood. An altered microbial metabolite profile plays a direct role in CRC metabolism. Furthermore, diet plays an essential role in the risk of gastrointestinal cancer development. High‑fiber diets regulate the gut microbiome and reduce the risk of CRC development, and may be fruitful in the better management of therapeutics. In the present review, the current status of the microbiome in CRC development is discussed.12

Multiple myeloma (MM), a clonal plasma cell disorder, disrupts the bones’ hematopoiesis and microenvironment homeostasis and ability to mediate an immune response against malignant clones. Despite prominent survival improvement with newer treatment modalities since the 2000s, MM is still considered a non-curable disease. Patients experience disease recurrence episodes with clonal evolution, and with each relapse disease comes back with a more aggressive phenotype. Bruton’s Tyrosine Kinase (BTK) has been a major target for B cell clonal disorders and its role in clonal plasma cell disorders is under active investigation. BTK is a cytosolic kinase which plays a major role in the immune system and its related malignancies. The BTK pathway has been shown to provide survival for malignant clone and multiple myeloma stem cells (MMSCs). BTK also regulates the malignant clones’ interaction with the bone marrow microenvironment. Hence, BTK inhibition is a promising therapeutic strategy for MM patients. In this review, the role of BTK and its signal transduction pathways are outlined in the context of MM.