The AACR Annual Meeting 2026 confirmed its role as a leading global forum in oncology, bringing together researchers, clinicians, and industry leaders to share cutting-edge advances across the full spectrum of cancer science. Below is a selection of key highlights from AACR 2026 expected to have a significant impact on precision oncology medicine in the coming years.
1-KRAS inhibition
KRAS is a small GTPase that is among the most commonly mutated oncogenes in cancer. KRAS inhibition has long been an unresolved challenge, until the development of first-generation G12C RAS mutant inhibitors sotorasib and adagrasib. Over the years, many other inhibitors have been developed and are being tested in clinical trials. Here are some examples of newly developed RAS inhibitors:
- Elisrasib, a new KRAS G12C inhibitor, has been investigated for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose disease progressed on previous immunotherapy and/or chemotherapy or first-generation KRAS G12C inhibitor therapy. Elisrasib treatment also resulted in clinical benefit for patients whose disease had progressed on first-generation KRAS G12C inhibitor therapy.
- KRAS G12D-mutated cancers are common, especially in pancreatic, colorectal, and lung cancer, and represent an area of large unmet need. Results of a Phase I clinical trial of zoldonrasib, a next-generation G12D-selective tri-complex RAS(ON) inhibitor that targets the active, GTP-bound state of KRAS, were presented. It works by forming a ternary complex with KRAS and blocking downstream signaling. The promising antitumor activity along with the favorable safety profile support the continued development of zoldonrasib as a single agent and in combination with other therapies.
- The development of novel classes of KRAS inhibitors (including degraders and tricomplex inhibitors) for combination therapy represents a promising strategy for overcoming resistance to existing agents.
2- Minimal residual disease (MRD)
While MRD has been used to personalize treatment in hematologic malignancies for decades, it is now an area of growing interest in solid tumors, thanks to advances in our understanding of MRD biology and our ability to detect it. Two distinct types of MRD are recognized in solid tumors: MRD after systemic therapy, which occurs in patients with advanced disease and is attributable to persister cells, and MRD after local surgery in patients with early-stage disease, due to microscopic metastases.
- During the transition from drug-tolerant persister cells to acquired resistance to targeted therapies and disease relapse in lung cancer, the mutator enzyme APOBEC3A—whose expression and activity are induced during treatment—plays a relevant role in driving genomic instability.
- Circulating tumor DNA (ctDNA) as a clinical tool for colorectal cancer patients’ selection based on MRD status for adjuvant chemotherapy trials. Actually, patient selection for adjuvant chemotherapy trials is currently guided by risk and not by the presence of disease, which results in treating many patients to benefit a few. Conversely, using circulating tumor DNA (ctDNA) as a clinical tool for patient selection based on MRD status would allow for enrichment of patients who will benefit from therapy, translating to a dramatic improvement in trial efficiency.
3- Proximity-inducing therapies
Proximity-inducing therapies are based on bifunctional small molecules or biologics to bring two biomolecules together—typically a target protein and an effector protein—to induce, destroy, or modify the target. Proximity-inducers can also be used to redirect transcription factors to promote expression of apoptotic genes or to disrupt the function of an essential cellular protein. Among them PROTACS (Proteolysis-targeting chimeras (PROTACs) bring a target protein into close proximity with an E3 ligase, prompting the cell to mark the target for destruction and Molecular Glues (Small molecules that modify protein surfaces to induce non-native interactions or stabilize existing protein-protein interactions)
- Proximity-inducing therapies are rapidly advancing, as seen by the recently reported success of the proximity-induced degrader daraxonrasib for pancreatic cancer.
- An investigational proximity-inducing compound called PCIP-1 has been shown to phenocopy the anticancer effects of PARP inhibitors in BRCA-deficient cells. The compound bridges PARP and BRD4 to induce PARP trapping onto DNA, leading to DNA repair inhibition and cell death, even in cells with acquired resistance to conventional PARP inhibitors.
Antibody-drug conjugates (ADCs)
ADCs are a class of therapeutics that use targeted monoclonal antibodies to deliver cytotoxic agents with precision.
- trastuzumab deruxtecan combination with the PARP inhibitor olaparib (Lynparza) in patients with advanced or recurrent HER2-positive uterine or ovarian tumors. After a median follow-up of 8.44 months, the six-month progression-free survival (PFS) rate was 88.2%. The confirmed objective response rate (ORR) was 46%.
- A CLDN6-targeting ADC evaluated in patients with platinum-resistant ovarian cancer led to an ORR of 52.9% and a DCR of 100%, with a favorable safety profile.
- A B7-H3-targeting ADC was administered in previously treated non-squamous non-small cell lung cancer patients without actionable genomic alterations, in combination with the immune checkpoint inhibitor adebrelimab, inducing an ORR of 47.1%, a DCR of 94.1%, and a median PFS of 14 months.
- The CD30 dual-payload antibody-drug conjugate (dpADC) designed to simultaneously deliver a microtubule inhibitor and a topoisomerase I inhibitor to overcome resistance to brentuximab vedotin, the first CD30-targeting ADC to be approved for the treatment of Hodgkin lymphoma and anaplastic large-cell lymphoma (ALCL). Treatment with CD30 dpADC showed preclinical activity both in Hodgkin lymphoma and ALCL tumor models and demonstrated improved tolerability compared with brentuximab vedotin.
- EPI-326, a tissue-selective EGFR bispecific antibody designed for the treatment of EGFR-driven cancers. This molecule simultaneously binds to EGFR and ITGB6, causing EGFR degradation at the disease site while sparing healthy tissue. EPI-326 treatment caused tumor regressions in EGFR-mutant and EGFR-wild type tumor models and was well tolerated.
Degraders
Several reports were presented on the therapeutic use of molecular glue degraders (see above for definition)
- TRI-611 is a selective molecular glue degrader of the ALK receptor tyrosine kinase, which is expressed as a fusion protein in approximately 5% of non-small cell lung cancer (NSCLC) cases. TRI-611 treatment induced dose-dependent ALK degradation and tumor shrinkage in NSCLC models, and caused tumor regression in an ALK-positive patient-derived tumor model and in intracranial tumor xenografts.
- The NEO-811, a potent and selective molecular glue degrader of the transcription factor ARNT (HIF-1β), which is involved in mediating cellular responses to hypoxia in the tumor microenvironment. NEO-811 treatment caused tumor regression in clear-cell renal cell carcinoma (ccRCC) xenograft models. NEO-811 is currently in clinical development for patients with locally advanced or metastatic unresectable ccRCC.
- A novel CD8 biased T-cell engager (AZD8359), targeting the novel prostate cancer antigen STEAP2, which has limited expression in normal tissue and high expression across all stages of prostate cancer. AZD8359 treatment induced antitumor activity in mouse models and caused reduced cytokine release compared with conventional T-cell engagers.
Patients With Pancreatic Cancer Treated With a Personalized mRNA Vaccine Alive Six Years Later
The long-term follow-up results from a phase I clinical trial evaluating a personalized mRNA vaccine to treat pancreatic cancer were presented. The vaccine is designed to recognize neoantigens unique to each patient’s cancer. Sixteen patients received the vaccine alongside atezolizumab (Tecentriq) and chemotherapy in the adjuvant setting. After a median of 4.2 years of follow-up, the eight patients with pancreatic cancer who had vaccine-induced T-cell responses to the vaccine had significantly prolonged survival compared to their counterparts who did not have responses to the therapeutic vaccine (3.4 years vs. not reached). Seven of the eight vaccine responders (87.5%) continue to be alive for six years after surgery, as compared with two of the nonresponders (25%).