A perspective on emerging therapies in metastatic colorectal cancer: Focusing on molecular medicine and drug resistance.

The majority of cancer cases are colorectal cancer, which is also the second largest cause of cancer-related deaths worldwide. Metastasis is the leading cause of death for patients with colorectal cancer. Metastatic colorectal cancer incidence are on the rise due to a tiny percentage of tumors developing resistant to medicines despite advances in treatment tactics. Cutting-edge targeted medications are now the go-to option for customized and all-encompassing CRC care. Specifically, multitarget kinase inhibitors, antivascular endothelial growth factors, and epidermal growth factor receptors are widely used in clinical practice for CRC-targeted treatments. Rare targets in metastatic colorectal cancer are becoming more well-known due to developments in precision diagnostics and the extensive use of second-generation sequencing technology. These targets include the KRAS mutation, the BRAF V600E mutation, the HER2 overexpression/amplification, and the MSI-H/dMMR. Incorporating certain medications into clinical trials has significantly increased patient survival rates, opening new avenues and bringing fresh viewpoints for treating metastatic colorectal cancer. These focused therapies change how cancer is treated, giving patients new hope and better results. These markers can significantly transform and individualize therapy regimens. They could open the door to precisely customized and more effective medicines, improving patient outcomes and quality of life. The fast-growing body of knowledge regarding the molecular biology of colorectal cancer and the latest developments in gene sequencing and molecular diagnostics are directly responsible for this advancement.

A dose-ranging study of labetalol in moderate to moderately severe hypertension.

Labetalol optimal doses for Indonesian patients were investigated in an open, multicentre, unforced titration dose-finding study involving 134 essential hypertensive outpatients with baseline supine DBP (SuDBP) of 105-129 mmHg. Labetalol was started at 50 mg bid and as necessary increased by 50 mg bid every 2 weeks. Evaluable for efficacy were 105 moderate and 25 moderately severe hypertensives. Labetalol was effective (decreased SuDBP to 90 mmHg or less) in 75% of patients and moderately effective (decreased SuDBP at least 10% of baseline but did not reach 90 mmHg) in 10%. The cumulative percent responders were 15, 49, 79 and 85% to final daily doses of 100, 200, 300 and 400 mg, respectively. Adverse reactions were found in 31% of patients, the most frequent were gastrointestinal complaints causing 3 withdrawals. It is concluded that labetalol optimal doses for Indonesian moderate to moderately severe hypertensives range from 100 to 300 mg daily in 2 divided doses.