Molecular effectors of radiation resistance in colorectal cancer

Evasion from apoptosis is critical for cancer development and progression. It is also a main reason for the resistance to anticancer therapy. Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer‐related mortality in the USA. Chemotherapy and radiation therapy are often combined with surgery to treat more advanced CRC patients. Although anticancer therapies have yielded a good success rate, the failure of treatment in over 90% of patients with advanced disease is due to resistance to the treatment, one of the biggest obstacles for effective cancer therapy. However, our knowledge of the molecular mechanisms that govern the resistance of CRC is very limited. No significant advance has been made to overcome the resistance. Therefore, there is an urgent need to identify molecules or pathways that can be targeted to overcome the resistance and improve cancer treatment. Expression of phosphatase of regenerating liver‐3 and survivin has been shown to correlate with advanced CRC, liver and lymph node metastases, high risk of recurrences, and worse patient survival. They have been implicated as important effectors in the resistance to anticancer therapy including radiation therapy in CRC. Their potential role in the resistance to radiation therapy makes them promising molecular targets to overcome radioresistance and increase efficacy of radiotherapy. The antagonists against phosphatase of regenerating liver‐3 and survivin could represent a novel type of molecular drug to be used in cancer treatment either as a single agent or, more likely, in combination with radiation or chemoradiation therapy.