Precision Oncology Across Cancer Types

Acute Myeloid Leukemia (AML) is a highly heterogeneous blood cancer with several genomic mutations that influence treatment decisions. FLT3 mutations occur in about 30% of cases and are associated with aggressive disease, but FLT3 inhibitors such as midostaurin and gilteritinib have improved outcomes. IDH1 and IDH2 mutations are also actionable, with targeted therapies like ivosidenib and enasidenib showing efficacy in blocking abnormal metabolic pathways. TP53 mutations, on the other hand, are linked to poor prognosis and resistance to standard chemotherapy, often leading to consideration of clinical trials. Next-generation sequencing (NGS) is critical in AML diagnosis, as it helps guide the selection of targeted treatments, stem cell transplant eligibility, and clinical trial enrollment. Precision oncology allows for more personalized and effective treatment approaches beyond traditional chemotherapy.

Bladder cancer is increasingly treated using precision oncology approaches, with FGFR3 mutations and fusions found in about 15-20% of cases, making patients eligible for FGFR inhibitors like erdafitinib. HER2 (ERBB2) mutations may also be present, offering a rationale for HER2-targeted therapies. PD-L1 expression levels guide immunotherapy selection, with checkpoint inhibitors such as atezolizumab and pembrolizumab being effective in advanced disease. For patients with DNA damage repair (DDR) gene mutations, such as ATM or BRCA2, PARP inhibitors may be considered, particularly in clinical trials. Biomarker-driven treatments help personalize bladder cancer therapy, increasing survival rates and reducing reliance on traditional chemotherapy. Comprehensive molecular profiling is recommended for advanced and metastatic cases to optimize treatment selection.

Glioblastoma (GBM) and other gliomas are aggressive brain tumors with limited treatment options, but genomic testing helps guide personalized therapy. IDH1 and IDH2 mutations, commonly found in lower-grade gliomas, are associated with better prognosis and may be targeted by IDH inhibitors. MGMT promoter methylation predicts a better response to temozolomide chemotherapy, while EGFR amplifications and alterations may indicate eligibility for targeted EGFR inhibitors in clinical trials. Additionally, BRAF V600E mutations, found in some gliomas, can be treated with BRAF/MEK inhibitors. Given the challenges of treating brain tumors, biomarker testing allows oncologists to refine treatment strategies, improve prognosis, and explore new targeted approaches through clinical trials.

Breast cancer treatment is increasingly guided by precision oncology, extending beyond traditional hormone receptor and HER2 status. PIK3CA mutations, present in about 40% of HR-positive/HER2-negative breast cancers, can be targeted with PI3K inhibitors like alpelisib. BRCA1 and BRCA2 mutations predict responsiveness to PARP inhibitors, which are particularly effective in triple-negative breast cancer. ESR1 mutations, which cause resistance to endocrine therapy, may guide treatment toward newer selective estrogen receptor degraders (SERDs). HER2-low tumors, a newly recognized category, may benefit from trastuzumab-deruxtecan (Enhertu). Comprehensive genomic testing helps refine therapy selection, reducing overtreatment and improving outcomes for different breast cancer subtypes.

Precision oncology is transforming cervical cancer treatment by identifying biomarkers that guide therapy selection. PD-L1 expression is a key factor in determining eligibility for immune checkpoint inhibitors like pembrolizumab, which have shown significant benefits in advanced or recurrent disease. Tumors with high tumor mutational burden (TMB) or microsatellite instability (MSI-H) may also respond well to immunotherapy. In rare cases, HER2 mutations can be found, offering the possibility of HER2-targeted therapies such as trastuzumab. Ongoing research is exploring the role of HPV-related molecular markers, which could open the door to new targeted treatments. By leveraging genomic profiling, patients with cervical cancer may access more effective, personalized therapies beyond standard chemotherapy and radiation.

Cholangiocarcinoma is a rare but aggressive cancer where precision oncology plays a critical role in treatment. FGFR2 gene fusions occur in up to 15% of cases and can be targeted with FGFR inhibitors like pemigatinib and futibatinib, which have shown promising results in advanced disease. IDH1 mutations, found in about 10-20% of patients, may respond to IDH1 inhibitors such as ivosidenib. BRAF V600E mutations, though less common, can be treated with BRAF/MEK inhibitors like dabrafenib and trametinib. Genomic testing is essential for cholangiocarcinoma patients, as it can identify actionable mutations that guide personalized treatment strategies and clinical trial opportunities, improving outcomes in this hard-to-treat cancer.

Biomarker testing in colorectal cancer (CRC) is crucial for guiding treatment decisions. KRAS, NRAS, and BRAF mutations determine eligibility for targeted therapies, with BRAF V600E-mutated tumors responding well to combination BRAF/MEK inhibitor regimens. MSI-H (microsatellite instability-high) and dMMR (deficient mismatch repair) status indicate strong potential for immune checkpoint inhibitors like pembrolizumab, offering an alternative to chemotherapy. HER2-positive CRC cases may benefit from HER2-targeted therapies, while NTRK fusions can be treated with TRK inhibitors such as Larotrectinib or entrectinib. Comprehensive molecular profiling is critical for optimizing therapy in metastatic CRC, allowing for more precise and effective treatment approaches.

Endometrial cancer treatment is increasingly guided by molecular subtyping and biomarker testing. MSI-H and POLE-mutated tumors respond well to immune checkpoint inhibitors, improving outcomes in patients with advanced disease. PTEN and PIK3CA mutations, common in endometrial cancer, suggest sensitivity to PI3K/AKT/mTOR inhibitors, while ERBB2 (HER2) amplifications may indicate eligibility for HER2-targeted therapies like trastuzumab. Identifying these genomic alterations allows for more tailored treatment, reducing reliance on conventional chemotherapy. Genomic testing is now an essential part of advanced endometrial cancer management, offering new opportunities for personalized medicine.

Esophageal cancer treatment is evolving with the integration of precision oncology. HER2-positive tumors respond well to HER2-targeted therapies such as trastuzumab, improving survival rates in HER2-amplified cases. PD-L1 expression is another critical biomarker that guides the use of immunotherapy with checkpoint inhibitors like nivolumab and pembrolizumab, especially in metastatic settings. Some tumors also harbor FGFR or MET alterations, which are being explored as potential therapeutic targets in clinical trials. By incorporating genomic profiling into standard care, oncologists can better tailor treatment strategies for esophageal cancer patients, optimizing outcomes and expanding therapeutic options.

Gastric cancer is increasingly managed using biomarker-driven therapies. HER2 overexpression, present in 10-20% of cases, allows for treatment with HER2-targeted drugs like trastuzumab. MSI-H tumors respond well to immunotherapy, particularly with checkpoint inhibitors, while FGFR2 and MET alterations may provide opportunities for targeted therapies. Claudin 18.2 (CLDN18.2) is emerging as a novel biomarker for treatment with monoclonal antibodies like zolbetuximab. Comprehensive molecular profiling ensures that gastric cancer patients receive the most effective, personalized therapies based on their tumor’s genetic profile.

Head and neck cancers can be stratified by molecular markers to guide treatment. HPV-positive tumors have a distinct biology and typically respond well to radiation and immunotherapy. EGFR overexpression may indicate potential benefit from EGFR inhibitors like cetuximab. PD-L1 expression levels are critical in determining eligibility for checkpoint inhibitors such as pembrolizumab or nivolumab. Emerging research is exploring additional genomic drivers, such as PIK3CA mutations, which may offer future targeted therapy options. Precision oncology is helping refine treatment approaches and improve survival in head and neck cancers.

Renal cell carcinoma (RCC) is increasingly treated with biomarker-based approaches. Mutations in VHL, MET, and PBRM1 guide therapy selection, with VEGF inhibitors and MET-targeted therapies playing key roles. PD-L1 expression and TMB status influence the use of immunotherapy, while genomic alterations in FH and SDH suggest eligibility for targeted therapies in rare RCC subtypes. Precision oncology allows for a more individualized approach, optimizing treatment and reducing unnecessary side effects.

Genomic testing in chronic lymphocytic leukemia (CLL) is essential for treatment decisions. TP53 mutations and IGHV status determine the effectiveness of chemotherapy, with TP53-mutated cases responding better to BTK inhibitors like ibrutinib. BTK and BCL2 mutations influence therapy resistance and guide drug selection, ensuring patients receive the most effective targeted treatments. Next-generation sequencing is crucial for monitoring disease progression and adapting treatment strategies in CLL.

Hepatocellular carcinoma (HCC) treatment is evolving with biomarker-driven approaches. High TMB and VEGF expression predict better responses to immunotherapy and VEGF inhibitors like bevacizumab. CTNNB1 and TP53 mutations are being investigated as potential targets for future therapies. Comprehensive molecular testing helps identify treatment options beyond conventional chemotherapy.

Non-small cell lung cancer (NSCLC) is one of the most genomically driven cancers, with mutations in EGFR, ALK, ROS1, BRAF, MET, RET, NTRK and KRAS guiding targeted therapies. EGFR inhibitors like osimertinib and ALK inhibitors like alectinib have significantly improved survival rates. PD-L1 expression influences the use of immunotherapy, making biomarker testing essential for treatment selection.

Next-generation sequencing plays a crucial role in identifying actionable mutations in Diffuse Large B-Cell Lymphoma (DLBCL). Patients with MYC, BCL2, and BCL6 rearrangements (double-hit or triple-hit lymphomas) often require more intensive therapy, such as R-CHOP with dose modifications or novel targeted agents. CD19 expression is essential for determining eligibility for CAR-T cell therapy, while EZH2 mutations can be targeted with EZH2 inhibitors like tazemetostat. NGS also helps identify rare subtypes, guiding the selection of clinical trials for emerging targeted therapies. Genomic profiling is becoming a standard tool to personalize treatment and improve outcomes in DLBCL.

Melanoma is highly driven by genomic mutations, making NGS-based testing critical for treatment selection. BRAF V600E mutations, present in about 50% of melanomas, enable the use of BRAF/MEK inhibitors like dabrafenib and trametinib, significantly improving survival. NRAS mutations, found in 15-20% of cases, may indicate sensitivity to MEK inhibitors. TMB (tumor mutational burden) and PD-L1 expression are key markers predicting response to immune checkpoint inhibitors, such as nivolumab and pembrolizumab. NGS also helps identify rare KIT mutations, which may respond to targeted therapies like imatinib. Molecular profiling is essential for guiding precision treatment in advanced melanoma.

Genomic testing, particularly NGS and homologous recombination deficiency (HRD) assays, is essential for optimizing ovarian cancer treatment. BRCA1/2 mutations predict response to PARP inhibitors like olaparib and niraparib, which significantly improve survival in advanced disease. HRD-positive tumors, even without BRCA mutations, may also benefit from PARP inhibition. PIK3CA and PTEN mutations suggest sensitivity to PI3K/AKT/mTOR inhibitors, while MSI-H tumors respond well to immunotherapy. Genomic profiling allows for tailored treatment strategies, helping oncologists determine which targeted therapies or clinical trials may be beneficial for each patient.

Pancreatic cancer has historically been difficult to treat, but NGS-based genomic testing has helped identify new therapeutic options. BRCA1/2 mutations and other DNA damage repair (DDR) gene alterations suggest responsiveness to PARP inhibitors like olaparib, particularly in maintenance therapy. KRAS mutations, present in a large majority of pancreatic cancers, are largely untargetable, but specific subtypes like KRAS G12C mutations may respond to KRAS inhibitors under clinical investigation. MSI-H and TMB-high tumors are eligible for immunotherapy, offering a new treatment avenue. Comprehensive genomic profiling is now a standard recommendation to personalize therapy in advanced pancreatic cancer.

Genomic testing, particularly through NGS-based liquid or tissue biopsy, plays a growing role in prostate cancer management. BRCA1/2 and ATM mutations indicate sensitivity to PARP inhibitors like olaparib, which are now approved for metastatic castration-resistant prostate cancer (mCRPC). AR-V7 (androgen receptor splice variant 7) mutations predict resistance to androgen receptor-targeting agents, such as enzalutamide, guiding the choice toward alternative therapies. Mismatch repair deficiencies (dMMR) and MSI-H tumors may respond to immunotherapy, while mutations in PTEN and PIK3CA suggest eligibility for PI3K/AKT-targeted therapies. Genomic profiling helps personalize treatment, improving outcomes for advanced prostate cancer.

Sarcomas are a diverse group of rare cancers, and genomic testing for sarcoma plays a crucial role in guiding personalized cancer treatment. Next-generation sequencing (NGS) helps identify actionable mutations such as KIT and PDGFRA alterations in gastrointestinal stromal tumors (GIST), which respond to tyrosine kinase inhibitors (TKIs) like imatinib. NTRK fusions, found in some soft tissue sarcomas, can be treated with TRK inhibitors such as larotrectinib. MDM2 amplifications in liposarcomas and ALK, ROS1, and FGFR1 mutations in rare sarcoma subtypes open opportunities for targeted therapies.