Exploiting NRF2-ARE pathway activation in papillary renal cell carcinoma.

Papillary renal cell carcinoma (pRCC) is the second most frequent renal cancer subtype but has no indicated targeted treatments. MET inhibition may be a treatment for MET-driven pRCC, but there is a large group of non-MET-driven pRCC without targeted therapy. Activation of NRF2-ARE pathway has been suggested to be involved in pRCC.

Multi-resolution deep learning characterizes tertiary lymphoid structures and their prognostic relevance in solid tumors.

Background: Tertiary lymphoid structures (TLSs) are dense accumulations of lymphocytes in inflamed peripheral tissues, including cancer, and are associated with improved survival and response to immunotherapy in various solid tumors. Histological TLS quantification has been proposed as a novel predictive and prognostic biomarker, but lack of standardized methods of TLS characterization hampers assessment of TLS densities across different patients, diseases, and clinical centers.

Methods: We introduce an approach based on HookNet-TLS, a multi-resolution deep learning model, for automated and unbiased TLS quantification and identification of germinal centers in routine hematoxylin and eosin stained digital pathology slides.

Biallelic ELOC-Inactivated Renal Cell Carcinoma: Molecular Features Supporting Classification as a Distinct Entity.

Approximately 70% of clear cell renal cell carcinoma (ccRCC) is characterized by the biallelic inactivation of von Hippel-Lindau (VHL) on chromosome 3p. ELOC-mutated (Elongin C-mutated) renal cell carcinoma containing biallelic ELOC inactivations with chromosome 8q deletions is considered a novel subtype of renal cancer possessing a morphologic overlap with ccRCC, renal cell carcinoma (RCC) with fibromyomatous stroma exhibiting Tuberous Sclerosis Complex (TSC)/mammalian Target of Rapamycin (mTOR) mutations, and clear cell papillary tumor. However, the frequency and consequences of ELOC alterations in wild-type VHL and mutated VHL RCC are unclear.

Altered cytoplasmic and nuclear ADP-ribosylation levels analyzed with an improved ADP-ribose binder are a prognostic factor in renal cell carcinoma.

ADP-ribosylation (ADPR) of proteins is catalyzed by ADP-ribosyltransferases, which are targeted by inhibitors (i.e. poly(ADP-ribose) polymerase inhibitors [PARPi]).

Analysis of the PARP1, ADP-Ribosylation, and TRIP12 Triad With Markers of Patient Outcome in Human Breast Cancer.

PARP inhibitors (PARPi) are increasingly used in breast cancer therapy, including high-grade triple-negative breast cancer (TNBC) treatment. Varying treatment responses and PARPi resistance with relapse currently pose limitations to the efficacy of PARPi therapy. The pathobiological reasons why individual patients respond differently to PARPi are poorly understood.