Main Findings: Engineering oncogene-containing extrachromosomal DNA generates preclinical immunocompetent mouse models of cancer. Concept: Cre-mediated recombination of a region flanked by loxP sites of the same orientation enable circularization and subsequent amplification under selection. Impact: This study advances preclinical modeling of human cancer that will inform the understanding of focal amplification–driven tumorigenesis.

The Chordoma Foundation and some of its philanthropic partners announced that they will launch a competition offering $500,000 in prizes for the discovery of drugs targeting the protein TBXT, a transcription factor long considered undruggable. TBXT is crucial for the development of the spinal cord and is commonly mutated in chordoma—a rare bone tumor that forms in the spine or skull—and in breast, lung, colon, and prostate tumors. Prizes of $250,000 and $100,000 will be awarded for compounds that bind TBXT, depending on the chemical affinity between the two molecules.

Cambridge, MA–based Mersana Therapeutics announced today that its B7-H4–targeted antibody–drug conjugate emilatug ledadotin (XMT-1660) elicited a complete response in 23% (six of 26) of patients with triple-negative breast cancer in a phase I trial. None of the patients, who had received a median of 4.5 prior therapies, developed grade 4 or 5 treatment-related adverse events (TRAE); the most common TRAEs were increases in liver enzymes and protein, experienced by 38% and 31% of patients, respectively. B7-H4 is a transmembrane glycoprotein expressed in low levels in normal tissues but upregulated in some solid tumors—notably cholangiocarcinoma and breast, ovarian, and endometrial cancers—and linked with a poor prognosis.

The FDA’s accelerated approval pathway allows for quicker access to drugs based on surrogate endpoints, such as progression-free survival. However, when considering new cancer drugs, patients are not always willing to forgo evidence of an overall survival benefit in favor of quicker access, according to a recent study.

Major Finding: Fasting-mimicking diet plus chemotherapy exhibits high response rates in triple-negative breast cancer. Concept: Tumors of complete responders exhibit an early downregulation of glucose metabolism genes and pathways. Impact: Early downregulation of glycolysis may be a predictive biomarker of response to fasting-mimicking diets.

Main Findings: Assessing selection for biallelic loss of tumor suppressor genes (TSG) reveals TSG zygosity as an important feature of cancer etiology. Approach: An allele-specific analysis of somatic TSG alterations was performed on tumors of 67 cancer types from over 48,000 patients. Impact: This study sheds light on mechanisms of TSG inactivation and proposes TSG zygosity as a predictive biomarker of response.

Of 3,066 patients with B-cell lymphoma, acute lymphoblastic leukemia, or multiple myeloma who received chimeric antigen receptor (CAR) T-cell therapy over a 6-year period, only one developed a T-cell cancer following treatment , according to a French study, suggesting that the risk of these malignancies after CAR T-cell therapy is very low ( Nat Med 2025 Jan 08 [Epub ahead of print] ). The patient was diagnosed with anaplastic lymphoma 3 years after receiving tisagenlecleucel (Kymriah; Novartis) for diffuse large B-cell lymphoma and was found to have an integration of a CAR transgene into a tumor suppressor gene. Concerns over secondary malignancies associated with CAR T-cell therapy prompted the FDA to require black box safety warnings on them last year, although other studies have also found only a minimal link between the therapy class and secondary cancers ( Cancer Discov 2024 Feb 01 [Epub] ) .

Main Findings: Complete blood count indices are patient-specific and stable over decades in healthy adults. Concept: These hematologic setpoints are deep physiological phenotypes associated with variation in clinical risk. Impact: A deeper understanding of patient-specific setpoints may inform the management of many common conditions, including myeloproliferative neoplasms.

Johnson & Johnson announced today that the combination of amivantamab (Rybrevant) and lazertinib (Lazcluze) showed a significant overall survival (OS) improvement compared with osimertinib (Tagrisso; AstraZeneca) in patients with non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R substitution mutations in the phase III MARIPOSA study. Amivantamab is a bispecific mAb targeting EGFR and MET, and lazertinib and osimertinib are both EGFR inhibitors; osimertinib is the standard-of-care for newly diagnosed patients with EGFR -mutated NSCLC. The relative improvement in median OS is expected to exceed 1 year, according to the company, which will report the specifics at an upcoming major medical meeting. Researchers already reported that patients receiving the combination had a median progression-free survival of 23.7 months, compared with 16.6 months in patients who received osimertinib ( Cancer Discov 2023;13:OF9 ).

Boston, MA–based Dana-Farber Cancer Institute (DFCI) today announced the launch of the Center for RAS Therapeutics , an initiative that aims to advance new treatments for patients with RAS -mutant cancers through collaborations between Dana-Farber researchers, industry, and other academic medical centers. RAS mutations are found in 20% of all cancers and are a major driver of certain malignancies, such as pancreatic and colorectal cancers. The program, which will support pre-clinical studies and clinical trials of RAS-directed therapies, will be directed by DFCI’s Chief of Strategic Partnerships Alice Shaw, MD, PhD, and Andrew Aguirre, MD, PhD, a gastrointestinal oncologist and pancreatic cancer researcher.

Main Findings: Visugromab, a GDF-15 blocking antibody, is tolerable and elicits clinical responses in combination with nivolumab. Concept: GDF-15 may represent a mechanism of anti-PD-1 resistance that can be targeted to enhance antitumor immunity. Impact: This phase I/IIa trial supports the safety and further clinical evaluation of this combination, particularly in NSCLC and urothelial cancer.

U.S. Surgeon General Vivek Murthy, MD, released an advisory today highlighting the link between alcohol consumption and cancer risk . After tobacco and obesity, alcohol use is the leading preventable cause of cancer in the United States, contributing to nearly 100,000 cases and 20,000 deaths annually, the advisory notes. However, less than half of U.S. adults are aware of the causal relationship between alcohol and cancer risk, which has been well-established for breast, colorectal, esophageal, liver, mouth, throat, and larynx cancers. The advisory makes several recommendations for reducing alcohol-related cancers, including updating the Surgeon General’s health warning label on alcoholic beverages to include a warning about cancer risks––a power that lies with Congress.

Innovent Biologics will license IBI3009 , its investigational DLL3-targeted antibody–drug conjugate (ADC) for small cell lung cancer (SCLC), to Roche for $80 million upfront and payments totaling up to $1 billion if development and commercialization milestones are reached. DLL3 is a cell-surface antigen expressed at high levels in certain cancers, including more than 80% of SCLCs. The first patient with SCLC received IBI3009 in a phase I trial in December 2024, which will also enroll patients with neuroendocrine carcinomas.

Basic and translational research shows that a low-carbohydrate, high-fat ketogenic diet, which is rich in the metabolite β-hydroxybutyrate, can increase the proliferation of chimeric antigen receptor T-cell therapies and better suppress tumor growth. Scientists have launched a phase I study to test their findings in patients.

In a phase II trial, the ROR1-targeting antibody–drug conjugate zilovertamab vedotin led to a complete response in nearly 100% of patients with diffuse large B-cell lymphoma.

Bristol Myers Squibb announced that the FDA approved nivolumab and hyaluronidase (Opdivo Qvantig) for subcutaneous injection across all currently approved solid tumor indications for intravenous (IV) nivolumab (Opdivo), including renal cell carcinoma, melanoma, non–small cell lung cancer, and numerous others. The PD-1 inhibitor plus hyaluronidase, which helps the body absorb injected drugs, can be used as a monotherapy or monotherapy maintenance treatment, or in combination with chemotherapy or cabozantinib (Cometriq; Exelixis), a multi-tyrosine kinase inhibitor. The decision was based on the phase III CheckMate 67T study, which pitted subcutaneous nivolumab and hyaluronidase against IV nivolumab in patients with small cell renal cell carcinoma; 24% of patients receiving both agents subcutaneously achieved an overall response, compared with 18% of those receiving nivolumab intravenously.

The anti-PD-1 mAb tislelizumab (Tevimbra; BeiGene) earned FDA approval for gastric and gastroesophageal junction cancers in combination with chemotherapy, following its approval earlier this year for patients with esophageal squamous cell carcinoma. The new approval is based on results from the phase III RATIONALE-305 study, in which 997 patients received either tislelizumab plus chemotherapy or placebo plus chemotherapy. Median overall survival was 15 months in the tislelizumab group and 12.9 months in the placebo group.

Major Finding: Tumor-connected neurons promote glioblastoma growth, invasion, and resistance to radiotherapy. Concept: Rabies virus–based retrograde tracing of neurons reveals their integration with glioblastoma cells. Impact: Disrupting neuron–tumor networks may enhance the efficacy of radiotherapy in glioblastoma.

Major Finding: Incorporating a modified CD3ε intracellular domain into a chimeric antigen receptor (E-CAR) improves signaling. Concept: E-CARs phase separate and form mature synapses that support sustained antitumor killing. Impact: This study informs the development of CAR T-cell therapies with enhanced antigen sensitivity and persistence.

After the U.S. Congress pulled funding for a few pediatric cancer programs from the bill passed last week to fund the government through March 14, the Senate voted unanimously to restore a $12.6 million annual allocation for childhood cancer research  for 5 years. The vote extends the Gabriella Miller Kids First Research Act, enacted in 2014 and named for a 10-year-old girl who died from an inoperable brain tumor, which directs funding to the NIH for pediatric cancer research. According to the act, the funding will support “important areas of emerging scientific opportunities, rising public health challenges, or knowledge gaps that deserve special emphasis.”  Because the U.S. House approved the funding extension last March, only the Senate needed to give the final approval.