Dr. Halfdanarson on Molecular Differences Between Left- Versus Right-Sided Tumors in CRC

Thorvardur (Thor) Halfdanarson, MD, an associate professor of medicine, Division of Medical Oncology; a medical oncologist; and an assistant program director for the Hematology/Oncology fellowship program at Mayo Clinic, discusses the molecular differences between left- versus right-sided tumors in colorectal cancer (CRC).

In terms of tumor sidedness, it has been known for a long time that right-sided tumors are more likely to be BRAF mutated, says Halfdanarson. Patients with BRAF-mutant tumors have a very poor prognosis compared with those who have BRAF wild-type tumors. More recently, it has also been confirmed that not all BRAF-mutanttumors are created equal. Different mutations exist within CRC, one of the most common being BRAF V600E, notes Halfdanarson. Other BRAF mutations, however, may be associated with prognosis in a different way; not all of them are associated with an inferior prognosis.

With the mismatch repair–deficient (dMMR) tumors, there is an interesting paradox, notes Halfdanarson. In general, right-sided tumors have a worse prognosis; this has been demonstrated in several trials. BRAF-mutant, right-sided tumors are also more likely to be dMMR, although that represents a relatively small proportion of all right-sided tumors. That small subgroup of patients with right-sided tumors responds well to immunotherapy, concludes Halfdanarson.