I love research and clinical applications in oncology that go beyond "the sequence" alone (e.g. recent unexpected work on chromothripsis, genomic instability, here, here.)
Here's an excellent article with a broad view of molecular oncology and its current puzzles. Find it in Nature Reviews Cancer, Wahida et al. Find it here (subscription).
- Timing. Is it critical to start precision therapies early, before multiple driver pathways accumulate?
- When is a mutation pathogenic? Which of several, in a tumor, is the most important driver? Why do some conditions (from adenomas to endometriosis - have "pathologic" mutations but are not cancer?
- Are mutations tissue-tropic? Such as BRAF having different impacts in different tissues of origin.
- Which tumor clone should be targeted? Are therapies "irrelevant" to some parts of the tumor?
- Are the roles of age, sex, microbiome bigger than we suspect?
- When, and based on what biomarkers, do we switch to immunotherapy? What about specific mutations (epitopes) rather than gross tumor mutation burden?