Time immunotherapy to the moment targeted drugs make tumours visible
Targeted drugs briefly make cancer cells easier for the immune system to spot. Giving immunotherapy exactly in that window, rather than at the same time, may work better.
MAPK and CDK4/6 inhibition transiently increase MHC class I expression, antigen presentation and interferon signalling, then this fades as resistance develops. Concurrent combinations have often been toxic and no more effective. Mass spectrometry immunopeptidomics and MHC imaging could define the window in patients, and immunotherapy could be scheduled to coincide with peak presentation rather than dosed continuously alongside.
- Acquired resistance to every therapy · Nearly every targeted therapy stops working within months to a few years as the tumour adapts.
- No one can predict who responds to immunotherapy · Checkpoint drugs cure some patients and do nothing for most. We still cannot tell the two apart before treating.
- Too many combinations to test · There are thousands of possible drug pairs and sequences. Trials can test a few dozen a year.
Pages like this
not linked directly; found by shared links- IdeaDesign drug pairs where resisting one makes you vulnerable to the other
Shares Too many combinations to test, RAS / RAF / MEK / ERK (MAPK), Acquired resistance to every therapy, Immune checkpoint inhibitors.
- IdeaRotate between drugs on a fixed schedule instead of waiting for failure
Shares Too many combinations to test, Acquired resistance to every therapy, HR-positive / HER2-negative breast cancer.
- InstitutionIstituto Oncologico Veneto IRCCS
Shares CDK4/6 inhibitors, Melanoma, Immune checkpoint inhibitors, HR-positive / HER2-negative breast cancer.
- IdeaCombination baskets defined by resistance mechanism rather than by cancer type
Shares CDK4/6 inhibitors, Too many combinations to test, Acquired resistance to every therapy.
- IdeaEradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells
Shares CDK4/6 inhibitors, Melanoma, HR-positive / HER2-negative breast cancer.
- IdeaRandomise a cheap antihistamine alongside immunotherapy
Shares No one can predict who responds to immunotherapy, Melanoma, Immune checkpoint inhibitors.
- Key paperLeach, Krummel and Allison: releasing the CTLA-4 brake makes mice reject tumours
Shares PD-1 / PD-L1 immune checkpoint & T-cell activation, No one can predict who responds to immunotherapy, Melanoma, Immune checkpoint inhibitors.
- PersonTasuku Honjo
Shares No one can predict who responds to immunotherapy, Melanoma, Immune checkpoint inhibitors.