Drug Resistance Mechanisms on Colorectal Cancer

Abstract

Standard treatment for colorectal cancer includes surgery, radiotherapy, and chemotherapy. Conventional chemotherapeutic agents used in colorectal cancer such as 5-fluorouracil, capecitabine which is oral form of 5-fluorouracil, irinotecan, and oxaliplatin. One of the major challenges in chemotherapy considered as drug resistance. Drug resistance occurs in many different mechanisms such as alteration in tumor microenvironment, growth kinetics, genetic variations, and tumor heterogeneity. These cytotoxic agents are used in combination form to overcome drug resistance on colorectal cancer. They can also be used in combination with cytotoxic agents as bevacizumab and cetuximab. Combination therapy depends on tumor burden, type, stage, and molecular characteristics. It is crucial to choose the combination therapy to be applied by taking these factors into consideration. In this review, current drug resistance mechanisms were discussed and then mechanisms of conventional chemotherapy related resistance were explained.

Affinities to Oxaliplatin: Vitamins from B Group vs. Nucleobases

“…The DNA replication and transcription are stopped, followed by the cell apoptosis [27]. Oxaliplatin is biotransformed through a number of spontaneous and non-enzymatic processes [28][29][30][31]. Nucleophiles, such as Cl − , HCO3 − , and H2O molecules, participate in these reactions (Figure 3) [30,32,33].…”

“…Oxaliplatin is biotransformed through a number of spontaneous and non-enzymatic processes [28][29][30][31]. Nucleophiles, such as Cl − , HCO3 − , and H2O molecules, participate in these reactions (Figure 3) [30,32,33]. In this way, several transient reactive species are formed, including dichloro-, monochloro-, and diaqua-DACH platin, which can complex with DNA and other macromolecules [30,32,33].…”

“…Nucleophiles, such as Cl − , HCO3 − , and H2O molecules, participate in these reactions (Figure 3) [30,32,33]. In this way, several transient reactive species are formed, including dichloro-, monochloro-, and diaqua-DACH platin, which can complex with DNA and other macromolecules [30,32,33]. Oxaliplatin belongs to the same group of Pt (II) derivatives used in cancer treatment, and it has a similar mechanism of action when compared to Cisplatin.…”

“…In this way, Oxaliplatin can interact with DNA and induce programmed cell death (Figure 2). Therefore, it can be assumed (analogously to Cisplatin) that the presence of other compounds possessing aromatic rings with electron lone pairs, such as N7 or/and N1 atoms, influences the therapeutic effect of the chemotherapeutic Oxaliplatin is biotransformed through a number of spontaneous and non-enzymatic processes [28][29][30][31]. Nucleophiles, such as Cl − , HCO 3 − , and H 2 O molecules, participate in these reactions (Figure 3) [30,32,33].…”

Utilising Proteomics and Organoid Cultures for Predicting Treatment Response in Colorectal Cancer

“…To deal with CRC progression and metastasis, different staging and classification systems together with different modes of treatment have been established throughout the years [4,5]. Despite the advancements made in therapeutic strategies, CRC mortality rate remains high, and development of chemoresistance due to different circumstances remains a major constraint to patients being treated [6][7][8].…”