Colorectal cancer (CRC) represents the third most frequent tumor and the fourth cause of cancer-related death in both men and women worldwide. Recent advances in CRC research have had a profound impact on changing the therapeutic approach. The study of Epidermal Growth Factor Receptors (EGFR) and downstream molecular pathways brought about new treatment options against metastatic CRC (mCRC): anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab, which block the activity of EGFR by preventing the binding with its natural ligands. However, as much as basic and clinical data accumulated, it had become clearer that not all patients would benefit from anti-EGFR-oriented interventions. CRC cells may bear a RAS or BRAF mutation conferring a ligand-independent activation of the EGFR pathway; this is the most frequent molecular mechanism of resistance to anti-EGFR mABs.
The treatment of patients with a RAS or BRAF mutation is therefore particularly challenging due to fewer therapeutic options available and a more aggressive tumor presentation. Anti-angiogenic drugs (bevacizumab and aflibercept) as well as chemotherapy triplet (folfoxiri) or new drugs (i.e. vemurafenib in BRAF V600E mutated patients) are currently explored and employed to treat RAS and BRAF mutated tumors. However, the high toxicity and/or the low clinical benefit of these treatments are still limiting the long-term outcomes of RAS or BRAF mutated mCRC patients.
This Research Topic will focus on the treatment of RAS or BRAF mutated mCRC patients. Original research and Review articles should present new data from clinical or basic research as well as analyze or discuss, with innovative and critical observations, previous research. Important topics to discuss include but are not limited to:
1) New approaches to the treatment of RAS or BRAF mutated mCRC.
2) New prognostic data on RAS or BRAF mutations: beyond the common hotspots.
3) The immune system and RAS or BRAF mutated mCRC.
Colorectal cancer (CRC) represents the third most frequent tumor and the fourth cause of cancer-related death in both men and women worldwide. Recent advances in CRC research have had a profound impact on changing the therapeutic approach. The study of Epidermal Growth Factor Receptors (EGFR) and downstream molecular pathways brought about new treatment options against metastatic CRC (mCRC): anti-EGFR monoclonal antibodies (mAbs) cetuximab and panitumumab, which block the activity of EGFR by preventing the binding with its natural ligands. However, as much as basic and clinical data accumulated, it had become clearer that not all patients would benefit from anti-EGFR-oriented interventions. CRC cells may bear a RAS or BRAF mutation conferring a ligand-independent activation of the EGFR pathway; this is the most frequent molecular mechanism of resistance to anti-EGFR mABs.
The treatment of patients with a RAS or BRAF mutation is therefore particularly challenging due to fewer therapeutic options available and a more aggressive tumor presentation. Anti-angiogenic drugs (bevacizumab and aflibercept) as well as chemotherapy triplet (folfoxiri) or new drugs (i.e. vemurafenib in BRAF V600E mutated patients) are currently explored and employed to treat RAS and BRAF mutated tumors. However, the high toxicity and/or the low clinical benefit of these treatments are still limiting the long-term outcomes of RAS or BRAF mutated mCRC patients.
This Research Topic will focus on the treatment of RAS or BRAF mutated mCRC patients. Original research and Review articles should present new data from clinical or basic research as well as analyze or discuss, with innovative and critical observations, previous research. Important topics to discuss include but are not limited to:
1) New approaches to the treatment of RAS or BRAF mutated mCRC.
2) New prognostic data on RAS or BRAF mutations: beyond the common hotspots.
3) The immune system and RAS or BRAF mutated mCRC.
