Promising New Agents for Colorectal Cancer

Abstract

Choosing the optimal treatment approach for patients with metastatic colorectal cancer (mCRC) demands that oncologists assess both clinical and genomic variables and individualize care based upon the findings. Clinically, choices depend on assessing the side of the colon in which the primary tumor originates, the sites and burden of metastatic disease, the patient's performance status, and their individual comorbidities. Genomic assessment of the tumor to discern the mutational status of genes such as RAS/RAF, HER2, and TRK, as well as assessing whether tumors have defective mismatch repair (dMMR) or high microsatellite instability (MSI-H), all factor in to potential treatment options and can determine clinical trial eligibility. Metastasectomy may be an option for patients with a low burden of disease and accessible liver- or lung-limited metastases. In some unresectable cases, systemic therapy with a FOLFOX- or FOLFIRI-based regimen with or without a biologic agent can lead to sufficient disease reduction to make a patient eligible for resection of metastatic disease. Tumor sidedness and RAS mutational status guide which biologic we add to the initial chemotherapy backbone, with patients with left-sided, RAS wild-type (WT) tumors receiving anti-epidermal growth factor receptor (EGFR)-directed therapy and patients with right-sided tumors or those with RAS mutations receiving bevacizumab. In patients with tumors that manifest microsatellite instability or deficient mismatch repair, we typically administer checkpoint inhibitors such as pembrolizumab or nivolumab after progression on irinotecan- or oxaliplatin-based therapies. In patients with progressive disease, we routinely send tumor tissue for next generation sequencing (NGS) to assess for the presence of actionable genomic alterations such as HER2, BRAF, and TRK fusions and offer them the option of enrollment on clinical trials with agents targeting those or other identified alterations.

Prognostic Value of SLC4A4 and its Correlation with Immune Infiltration in Colon Adenocarcinoma

“…DNA mismatch repair is one of the main causes of colon adenocarcinoma [ 28 ]. Checkpoint inhibitors such as pembrolizumab and nivolumab after progression on irinotecan- or oxaliplatin-based therapies may benefit patients who exhibit DNA mismatch repair [ 29 ]. This imbalance in base excision repair may determine treatment response of colon adenocarcinomas and may be prognostic for survival [ 30 , 31 ].…”

A Novel T Cell-Engaging Bispecific Antibody for Treating Mesothelin-Positive Solid Tumors

“…Both RG7802 and EM801 produce minimal nonspecific T-cell activation in the absence of target cells. In clinical trials, anti-CEA/CD3 (RG7802) and EM801 exhibited manageable toxicities [22,43]. MG1122-A was generated by combining anti-MSLN scFab on the knob arm and anti-CD3 scFab on the hole arm.…”

Cisplatin is more mutagenic than carboplatin or oxaliplatin at equitoxic concentrations

“…Carboplatin is as effective as cisplatin in the treatment of ovarian cancer, but it is better tolerated (16), whereas it shows no clear tolerability benefit over cisplatin in the treatment of lung cancer (17). The third-generation platinum-derived antitumor drug oxaliplatin, which obtained FDA approval in 1996, is mainly used in colorectal cancer in combination therapy (18)(19)(20). Oxaliplatin has lower toxicity than cisplatin (21); it shows very limited activity against cisplatin-resistant tumours (22).…”