Future therapeutic implications of new molecular mechanism of colorectal cancer

Abstract

High incidence (10.2%) and mortality (9.2%) rates led to the ranking of colorectal cancer (CRC) as the second most malignant tumor spectrum worldwide in 2020. Treatment strategies are becoming highly dependent on the molecular characteristics of CRC. The classical theories accept two models depicting the origin of CRC: The progression of adenoma to cancer and transformation from serrated polyps to cancer. However, the molecular mechanism of CRC development is very complex. For instance, CRCs originating from laterally spreading tumors (LST) do not adhere to any of these models and exhibit extremely serious progression and poor outcomes. In this article, we present another possible pathway involved in CRC development, particularly from LST, with important molecular characteristics, which would facilitate the design of a novel strategy for targeted therapy.

Discovery of a Novel CSF-1R Inhibitor with Highly Improved Pharmacokinetic Profiles and Superior Efficacy in Colorectal Cancer Immunotherapy

“…The organic phase was combined and washed with brine, dried over anhydrous Na 2 SO 4 , and evaporated under vacuum to give intermediate 3a as a dark green solid (0.80 g, yield: 62%). 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm): 10.10 (1H, s), 6.79 (1H, d, J = 8.5 Hz), 6.10 (1H, d, J = 2.0 Hz), 6.09 (1H, dd, J 1 = 5.5 Hz, J 2 = 3.6 Hz) 5.01 (2H, s), 3.24 (2H, s).…”

“…Yellow solid, 75% yield, mp: >300 °C. 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm): 13.75 (1H, s), 10.97 (1H, s), 9.50 (1H, s), 8.91 (1H, s), 7.71 (1H, d, J = 8.2 Hz), 7.55 (1H, s), 7.30 (1H, d, J = 1.8 Hz), 6.91 (1H, dd, J 1 = 8.2 Hz, J 2 = 2.0 Hz), 6.51 (1H, s), 4.22 (2H, q, J = 7.1 Hz), 2.54 (3H, s), 2.48 (3H, s), 1.33−1.28 (12H, m). 13 C NMR (126 MHz, DMSO-d 6 ) δ (ppm): 180.7, 170.4, 164.9, 158.8, 151.6, 140.0, 139.8, 138.6, 131.3, 126.6, 122.0, 120.2, 120.0, 117.3, 113.6, 111.9, 100.7, 92.9, 59.5, 33.0, 28.8 (3C), 15.0, 14.8, 11.8.…”

“…Yellow solid, 85% yield, mp: >300 °C. 1 H NMR (500 MHz, DMSOd 6 ) δ (ppm): 13.71 (1H, s), 10.97 (1H, s), 9.51 (1H, s), 8.92 (1H, s), 7.90 (1H, s), 7.73 (1H, d, J = 8.2 Hz), 7.62 (1H, s), 7.32 (1H, d, J = 2.0 Hz), 6.92 (1H, dd, J 1 = 8.2 Hz, J 2 = 2.0 Hz), 6.52 (1H, s), 2.43 (3H, s), 1.30 (9H, s). 13 , d, J = 1.9 Hz), 6.90 (1H, dd, J 1 = 8.2 Hz, J 2 = 1.9 Hz), 6.52 (1H, s), 1.30 (9H, s).…”

“…Yellow solid, 85% yield, mp: >300 °C. 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm): 10.57 (1H, s), 9.51 (1H, s), 9.04 (1H, s), 8.26 (1H, d, J = 8.4 Hz), 8.11 (1H, d, J = 1.6 Hz), 7.37 (1H, d, J = 2.0 Hz), 7.20 (1H, s), 7.19 (1H, d, J = 3.4 Hz), 6.86 (1H, dd, J 1 = 8.5 Hz, J 2 = 2.0 Hz), 6.79 (1H, dd, J 1 = 3.4 Hz, J 2 = 1.8 Hz), 6.52 (1H, s), 1.31 (9H, s). 13 (…”

“…Colorectal cancer (CRC) is the second leading cause of death in the world, and its incidence is increasing and getting younger. 1,2 Although current therapies such as surgery combined with chemotherapy can prolong the survival of CRC patients, the 5-year survival rate of advanced patients is still less than 20%. Some targeted drugs significantly improve patient survival, but the problem of drug resistance leads to high recurrence rates.…”