Molecularly targeted therapy articles from across Nature Portfolio

Renal cell carcinoma is a metabolic disease linked to a variety of alterations in genes that regulate cellular metabolism. Here, the authors examine cell-intrinsic metabolic alterations in hereditary and sporadic renal cell carcinoma, and how they can be exploited to develop novel therapeutic interventions.

According to the precision oncology paradigm, cancer therapies are increasingly being matched to specific sensitizing alterations using a biomarker-directed approach. However, the criteria for determining the actionability of molecular alterations and selecting matched treatments evolve over time. Molecular tumour boards (MTBs) have emerged as means to capitalize on the collective knowledge of various experts to interpret molecular-profiling data and to eliminate subjectivity in treatment selection. This Review describes the components, processes and increasingly important role of MTBs in optimizing the implementation of precision oncology in both clinical trials and clinical practice, as well as current and future considerations for ensuring the sustainability of MTBs and expanding their outreach to underserved populations.

The complement system is often involved in immune-driven kidney injury. In this Review, the authors discuss complement activation in a variety of kidney diseases, including conditions not traditionally considered to be immune-mediated, and the potential of complement therapeutics for the treatment of kidney disease.

Several successfully completed clinical trials of novel therapies in glomerular disease were reported in 2023. Building on important mechanistic discoveries about disease onset and progression over the past several years, these therapies raise hope that multiple options will be available to reduce the risk of kidney failure in glomerular disease.

Recent results from the phase III PHILA trial demonstrate a benefit in terms of progression-free survival derived from the addition of pyrotinib to first-line chemotherapy plus trastuzumab in patients with metastatic HER2-positive breast cancer. Dual HER2 blockade with pyrotinib and trastuzumab is an effective therapeutic strategy but might increase the risk of gastrointestinal toxicity; therefore, the risk-to-benefit ratio should be carefully evaluated.