Alterome Therapeutics: Innovative Targets and Research

Alterome Therapeutics is advancing precision medicine by developing drugs for genetically defined cancers. By targeting specific molecular alterations, the company aims to create therapies that are more effective and less toxic than conventional treatments.

With a foundation in cutting-edge research, Alterome leverages specialized platforms to accelerate discovery and development.

Targeted Molecular Pathways

Alterome Therapeutics focuses on molecular pathways that drive tumorigenesis in genetically defined cancers. By targeting oncogenic mutations, the company seeks to disrupt aberrant signaling cascades that fuel tumor growth while minimizing off-target effects. One key area of focus is receptor tyrosine kinases (RTKs), which regulate cell proliferation, differentiation, and survival. Mutations in RTKs, such as EGFR, ALK, and RET, are implicated in malignancies including non-small cell lung cancer (NSCLC) and thyroid carcinoma. Small-molecule inhibitors designed to selectively bind mutated RTKs have demonstrated efficacy in clinical trials, offering a more tailored approach to treatment.

Beyond RTKs, Alterome is exploring serine/threonine kinases involved in the MAPK and PI3K/AKT/mTOR pathways. Dysregulation of these networks drives unchecked cellular proliferation and resistance to apoptosis in many solid tumors. Targeting downstream effectors such as MEK and AKT has shown promise in overcoming resistance mechanisms. For instance, dual inhibition of MEK and ERK has enhanced tumor regression in BRAF-mutant melanoma, highlighting the potential of pathway-specific interventions.

Another focus is synthetic lethality, which exploits genetic dependencies unique to cancer cells. By identifying tumor-specific vulnerabilities, researchers can develop drugs that selectively induce cell death while sparing normal tissues. A well-documented example is PARP inhibition in BRCA-mutated cancers, which has led to FDA-approved therapies for ovarian and breast cancer. Alterome is applying this approach to other oncogenic drivers, aiming to expand synthetic lethal interactions beyond current targets.

Research Platforms

Alterome employs specialized research platforms to accelerate precision oncology drug development. These platforms integrate computational modeling, high-throughput screening, and structure-based drug design to identify small molecules with high specificity for oncogenic mutations. Advanced bioinformatics and machine learning help predict structural conformations of mutant proteins, enabling the rational design of selective inhibitors. This computational approach streamlines lead optimization and enhances the likelihood of developing compounds with favorable pharmacokinetic properties.

Functional genomics plays a key role in identifying genetic dependencies in cancer cells. Through CRISPR-based gene editing and RNA interference screens, researchers pinpoint vulnerabilities unique to tumor cells with specific mutations. These insights guide drug development by uncovering novel synthetic lethal interactions. Genome-wide CRISPR screens, for example, have revealed previously unrecognized dependencies in KRAS-mutant cancers, informing the design of targeted inhibitors.

To validate candidate molecules, Alterome integrates patient-derived tumor models into its research pipeline. Organoids and xenografts provide a physiologically relevant environment to assess drug efficacy and resistance mechanisms. Using genetically profiled tumor samples, researchers evaluate how targeted agents perform in heterogeneous cancer populations, improving the translational relevance of preclinical findings. This approach has been particularly valuable in predicting response rates for inhibitors targeting rare oncogenic fusions, which often lack robust clinical datasets.

Disease Categories In Focus

Alterome prioritizes malignancies driven by well-defined genetic alterations, particularly those with limited treatment options or high resistance rates. NSCLC remains a central focus due to the prevalence of actionable mutations such as EGFR, ALK, and ROS1 rearrangements. While targeted therapies have improved outcomes, acquired resistance—often through secondary mutations or bypass signaling—continues to pose a challenge. Alterome is developing inhibitors to address resistance mechanisms, aiming to extend treatment durability and delay disease progression.

Beyond lung cancer, the company is investigating therapeutic strategies for colorectal and pancreatic cancers, both of which frequently exhibit KRAS mutations. Historically considered “undruggable” due to its smooth surface and lack of deep binding pockets, KRAS has recently become a viable target with covalent inhibitors specific to the G12C mutation. However, other KRAS variants, such as G12D and G12V, remain difficult to treat. Alterome is working to develop small molecules that selectively inhibit a broader range of KRAS mutations, addressing gaps left by current treatments.

Hematologic malignancies are another area of interest, particularly acute myeloid leukemia (AML) and multiple myeloma, where genetic drivers such as FLT3-ITD and t(11;14) translocations contribute to aggressive disease progression. While FLT3 inhibitors have shown efficacy in AML, resistance frequently emerges through secondary mutations or compensatory signaling. Alterome is developing next-generation inhibitors with improved selectivity and potency to suppress both primary oncogenic drivers and resistance-associated variants.

Publication Highlights

Alterome Therapeutics has contributed to the scientific community through publications highlighting advancements in precision oncology. Recent articles in Cancer Discovery and Nature Reviews Drug Discovery detail the company’s innovative approaches to overcoming resistance mechanisms in kinase-driven cancers. These publications emphasize structure-based drug design strategies that enhance binding specificity and minimize off-target toxicity, improving patient outcomes.

A study in The Journal of Clinical Investigation explored a next-generation kinase inhibitor targeting secondary resistance mutations in EGFR-mutant lung cancer. Preclinical data showed the compound maintained potency against tumors harboring T790M and C797S mutations, two common resistance alterations following first-line EGFR inhibitor therapy. The study also underscored the importance of pharmacokinetic optimization, demonstrating that sustained drug exposure correlated with prolonged tumor suppression in patient-derived xenograft models.