Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers.

Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12-15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, leaving patients with limited options.

Wnt/β-Catenin Inhibition Disrupts Carboplatin Resistance in Isogenic Models of Triple-Negative Breast Cancer.

Triple-Negative Breast Cancer (TNBC) is the most aggressive breast cancer subtype, characterized by limited treatment options and higher relapse rates than hormone-receptor-positive breast cancers. Chemotherapy remains the mainstay treatment for TNBC, and platinum salts have been explored as a therapeutic alternative in neo-adjuvant and metastatic settings. However, primary and acquired resistance to chemotherapy in general and platinum-based regimens specifically strongly hampers TNBC management.

Genomic Characterisation and Response to Trastuzumab and Paclitaxel in Advanced or Recurrent HER2-positive Endometrial Carcinoma.

Background/aim: Human epidermal growth factor receptor 2 (HER2) positivity is associated with a worse prognosis in endometrial cancer (EC). Trastuzumab as a single agent did not demonstrate activity in such cases but there are no reports on its combined use with taxanes. We report the outcome in patients treated simultaneously with trastuzumab and paclitaxel for advanced or recurrent HER2-positive endometrial carcinoma and compared it to their microsatellite instability (MSI) status and PIK3CA mutational profiles.

The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts.

Several questions about the role of the oxygen sensor prolyl-hydroxylase 2 (PHD2) in cancer have not been addressed. First, the role of PHD2 in metastasis has not been studied in a spontaneous tumor model. Here, we show that global PHD2 haplodeficiency reduced metastasis without affecting tumor growth.

Endothelial cell metabolism: parallels and divergences with cancer cell metabolism.

The stromal vasculature in tumors is a vital conduit of nutrients and oxygen for cancer cells. To date, the vast majority of studies have focused on unraveling the genetic basis of vessel sprouting (also termed angiogenesis). In contrast to the widely studied changes in cancer cell metabolism, insight in the metabolic regulation of angiogenesis is only just emerging.

Angiogenesis revisited - role and therapeutic potential of targeting endothelial metabolism.

Clinically approved therapies that target angiogenesis in tumors and ocular diseases focus on controlling pro-angiogenic growth factors in order to reduce aberrant microvascular growth. Although research on angiogenesis has revealed key mechanisms that regulate tissue vascularization, therapeutic success has been limited owing to insufficient efficacy, refractoriness and tumor resistance. Emerging concepts suggest that, in addition to growth factors, vascular metabolism also regulates angiogenesis and is a viable target for manipulating the microvasculature.

The multifaceted activity of VEGF in angiogenesis - Implications for therapy responses.

Vascular endothelial growth factor (VEGF) is a key growth factor driving angiogenesis (i.e. the formation of new blood vessels) in health and disease.

Tumor vessel normalization by chloroquine independent of autophagy.

Chloroquine (CQ) has been evaluated as an autophagy blocker for cancer treatment, but it is unknown if it acts solely by inhibiting cancer cell autophagy. We report that CQ reduced tumor growth but improved the tumor milieu. By normalizing tumor vessel structure and function and increasing perfusion, CQ reduced hypoxia, cancer cell invasion, and metastasis, while improving chemotherapy delivery and response.