Innovative therapies for prostate cancer treatment

Androgen ablation is effective therapy for metastatic prostate cancer, but the majority of men eventually become refractory to this intervention. Cytotoxic chemotherapy offers palliation to symptomatic patients with hormone-refractory prostate cancer (HRPC); however, no chemotherapy regimen has yet been shown to prolong survival. There is a clear need for new agents and drug targets for the treatment of HRPC. A number of innovative therapeutic approaches that are rationally based and target driven are under investigation. This article reviews the development of antisense oligonucleotides that inhibit the anti-apoptotic bcL-2 protein. Approaches that target the epidermal growth factor receptor, the platelet derived growth factor receptor, and nuclear factor kappa-B are also discussed. There is much expectation that these therapies alone or in combination with cytotoxic chemotherapy will impact the clinical outcome of patients with HRPC.     

Controversy: PPARgamma as a target for treatment of colorectal cancer

Colorectal cancer (CRC) represents a significant cause of morbidity and mortality worldwide. Recently, ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) have exhibited promise in the treatment of CRC. For example, activation of PPARgamma reduces the proliferation of cultured CRC cells grown in vitro or in vivo using the nude mouse xenograft model of tumor growth. Furthermore, agonists of the receptor also reduce the development of preneoplastic lesions in a model of carcinogen-induced CRC in rats. However, ligands for the receptor paradoxically enhance intestinal adenoma formation in another murine model of intestinal polyposis, the APC(Min) mice. These disparate results may be due to the inherent limitations of the APC(Min) mouse as a model for humans with CRC. Finally, genetic studies identifying loss of function mutations of PPARgamma in human CRC specimens strongly suggest a tumor suppressive role for the receptor during the development of CRC.     

General treatment for metastatic colorectal cancer: From KEYNOTE 177 study

In the palliative treatment of metastatic colorectal cancer (mCRC), doublet chemotherapy (FOLFOX or FOLFIRI) or triplet chemotherapy (FOLFOXIRI) combined with targeted drugs (cetuximab or bevacizumab) is the main regimen. Recently, microsatellite instability-high (MSI-H) or DNA mismatch repair deficient (dMMR) was discovered as a biomarker to distinguish immunotherapy-benefited populations. In this context, recently published randomized phase III clinical trials tested the efficacy and safety of immunotherapy and traditional chemotherapy with or without targeted drugs as first-line treatment for patients with MSI-H/dMMR mCRC.Here, we briefly analyze this article and further discuss immune monotherapy or double immunotherapy for patients with MSI-H/dMMR mCRC, the immunotherapy for patients with BRAF V600E mutant mCRC, and the immunotherapy for patients with microsatellite stable mCRC.