Twelve early-career researchers who embarked on their independent research paths in 2024 reflect on their experience from their journey so far, describe the opportunities they received and the challenges they faced, and share their hopes and plans for the future.

T cell therapies for solid tumors took center stage, while new small-molecule drugs now offer targeted options for hard-to-treat cancers.

Rudalska et al. describe a novel class of p38α inhibitors with increased target residence time. They explore the drugs’ specificity, pharmacokinetics and toxicity profile and show that they are efficacious in the context of colorectal cancer.

Rinnerthaler et al. perform a randomized phase 2 trial of neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in patients with early HER2-positive breast cancer and report positively on efficacy and safety.

Panzeri et al. use a Trim28^+/D9 mouse model with intrinsic developmental heterogeneity to show that ‘heavy’ and ‘light’ developmental morphs exhibit different timing, type and severity of cancer, linked to a relevant DNA hypomethylation signature.

Sanlorenzo et al. propose a strategy to boost immunotherapy by combining topically applied TLR7/8 agonists with systemic interferon-I, sensitizing dendritic cells to produce IL-12 for tumor clearance and an adaptive immune response at metastatic sites.

Whalen et al. report that increased DNA end resection in BRCA-deficient, PARP inhibitor-resistant cancers leads to increased sensitivity to DNA nicks, limiting tumor formation in mice, and propose the therapeutic exploration of nickases.

Puigserver and colleagues show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of antigen-processing and presentation components.

Rudalska et al. describe a novel class of p38α inhibitors with increased target residence time. They explore the drugs’ specificity, pharmacokinetics and toxicity profile and show that they are efficacious in the context of colorectal cancer.

Rinnerthaler et al. perform a randomized phase 2 trial of neoadjuvant atezolizumab in combination with dual HER2 blockade plus epirubicin in patients with early HER2-positive breast cancer and report positively on efficacy and safety.

Training the next generation of cancer researchers is essential for the cancer research enterprise. However, training programs and methods to evaluate their effectiveness vary greatly across the USA and other countries. Here we discuss strategies to enhance cancer education and processes by which training may be standardized.