Precision Medicine in Oncology®

After nearly two decades of successfully developing therapies directed at molecular aberrations in non–small cell lung cancer, investigators are exploring a new generation of novel targets, including some not specifically associated with driver mutations.

Sonam Puri, MD, discusses the rationale to evaluate the real-world multiomic characterization of small cell lung cancer subtypes.

Hirva Mamdani, MD, discusses the rationale to evaluate the immunogenicity of STK11 and TP53 co-mutations in non–small cell lung cancer.

Abdul Rafeh Naqash, MD, discusses the results of a tumor profiling study in STK11 and TP53 co-mutated non–small cell lung cancer.

Osimertinib has emerged as the standard of care for patients with EGFR-mutated non–small cell lung cancer, but the need for novel agents is underscored as disease progression on the agent is inevitable.

Sukhmani K. Padda, MD, discusses strategies to overcome EGFR resistance in patients with non–small cell lung cancer.

Bispecific antibodies have become an interesting new class of agents in the lung cancer pipeline, most recently with the developments of amivantamab-vmjw, zenocutuzumab, and tarlatamab.

Dr. George and Dr. Hurley discuss the data generated from their study on the correlation between deleterious variants in genes and the development of hereditary breast and ovarian cancers in populations throughout the Caribbean.

Drs Brown and Husain discuss the current and future applications of next-generation sequencing in lung cancer, the role of tissue-based testing in light of the growing role for liquid-based testing, and some of the emerging technologies that could overcome current barriers to biomarker testing.

Multicancer early detection tests yielded high specificity and accuracy in predicting cancer signal origin and identified cancer signals in multiple tumor types.

The FDA has approved the FoundationOne Liquid CDx for use as a companion diagnostic to assist in the identification of patients with metastatic non–small cell lung cancer whose tumors harbor MET exon 14 skipping mutations and who could derive benefit from treatment with capmatinib.

The lead novel candidate, the WEE1 inhibitor adavosertib, has been tested in more than 50 completed or ongoing clinical studies but has yet to proceed to a phase 3 trial despite showing promising safety and efficacy as monotherapy and in combination with a range of other cancer therapies.

During the past decade, a growing number of PD-1/PD-L1 inhibitors gained FDA approval to treat a wide range of cancer types. Their stimulatory counterparts also emerged as sought-after anticancer targets but have proved much more challenging to manipulate therapeutically.

The FDA has approved FoundationOne CDx for use as a companion diagnostic for brigatinib, which was approved for the treatment of adult patients with ALK-positive, metastatic non–small cell lung cancer.

NRG1 fusions, which are often first detected by RNA-based sequencing, confer a more molecularly, pathologically, and clinically diverse subtype of lung cancer compared with historical hypotheses.

Next-generation sequencing plays a critical role in the diagnosis of patients with myeloid malignancies, but it also plays a necessary role in the identification of passenger mutations and subclonal events that go beyond founding drivers.

Streamlined processes afforded by in-house genomic testing have the potential to provide clinical, collaborative, and financial benefits.

Alison Schram, MD, discusses the results of the phase 1/2 eNRGy trial, which were presented during the 2021 ASCO Annual Meeting, in NRG1 fusion–positive solid tumors.

Several distinct subgroups have been identified within the myelodysplastic syndrome genomic landscape and have notable clinical features and discrete evolution patterns that provide proof of concept for next-generation disease classification and prognosis.

Dual blockade of the RAF/MEK and FAK pathways presents an opportunity for investigators to enhance and expand the number of patients with recurrent low-grade serous ovarian cancer who can benefit from targeted therapies.

Multiple FDA approvals and an increasing number of clinical trials examining molecular target–based therapeutics, including second- or even third-generation drugs against a well-defined target, present an ever-widening array of drugs for routine cancer care based on the discovery of specific molecular targets within the tumor or within the germline.

Among the pioneering targets for antibody therapy was CD20, the pursuit of which ultimately led to the first FDA-approved mAb for cancer therapy, rituximab, and defined a new era in the management of B-cell malignancies.

Kaiku Health has announced that they are partnering with the global healthcare company Novartis to develop a digital patient monitoring and management system specifically for patients with melanoma who are receiving BRAF/MEK combination therapies.

Dr. Pant discusses the current role for germline and somatic testing in pancreatic cancer, examines the research landscape with PARP inhibitors, KRAS inhibitors, and other targeted agents, and shares his hope for the future of drug development in the field.

In an effort to build on the efficacy demonstrated with ruxolitinib, investigators are evaluating combination therapies—specifically the dual inhibition of the JAK-STAT and BET pathways using pelabresib, a novel BET inhibitor.