Following on from news of Mercks $USD 32bill pitch for Revolution Medicine who have a KRAS gene inhibitor ( see
@nathiter post
https://hotcopper.com.au/threads/industry-news.6069623/page-3361?post_id=82340277 )
I asked Chatgpt "From a commercial perspective which oncogene has the most potential if able to be inhibited?" and this is what she said.
(TL;DR
@LongTony might be correct in his valuations
)
Executive answer (short)
Highest absolute commercial upside:MYC
Best proven risk-adjusted oncology returns today:KRAS
Largest future “step-change” opportunity if cracked:MYC
Most impactful across oncology and non-oncology:MYC
If a true MYC inhibitor works in humans with acceptable safety, it would likely be one of the most valuable drug classes ever created.
Why MYC is the #1 commercial prize
1. MYC sits at the top of cancer biology
MYC is not just “another oncogene”:
It is a master regulator controlling proliferation, metabolism, ribosome biogenesis, replication stress, and survival.
It is dysregulated in ~50–70% of human cancers, either directly (amplification/overexpression) or functionally (pathway convergence).
Many cancers are MYC-dependent, even when MYC itself is not mutated.
Commercial implication:
A MYC inhibitor is tumor-agnostic by biology, not just by label.
2. MYC unlocks multiple revenue pillars
If MYC inhibition is proven:
| Revenue pillar | Why it matters |
|---|
| 1 | Broad oncology monotherapy | Multiple solid + hematologic cancers |
|---|
| 2 | Combination backbone | Sensitizes tumors to chemo, TKIs, PARP, IO |
|---|
| 3 | Resistance breaker | MYC drives resistance to targeted therapies |
|---|
| 4 | Earlier-line use | Potential movement into 1L/2L settings |
|---|
| 5 | Non-oncology expansion | Fibrosis, proliferative diseases (with care) |
|---|
No other oncogene offers this many monetizable angles simultaneously.
3. MYC vs other major oncogenes (commercial lens)
| Oncogene | Commercial upside if inhibited | Why / why not |
|---|
| 1 | MYC | ⭐⭐⭐⭐⭐ (exceptional) | Central hub, massive prevalence, combo + non-cancer potential |
|---|
| 2 | KRAS | ⭐⭐⭐⭐ | Huge success already, but mutation-specific and competitive |
|---|
| 3 | EGFR | ⭐⭐⭐ | Mature market, resistance common, incremental upside |
|---|
| 4 | BRAF | ⭐⭐ | Narrow biology, saturated |
|---|
| 5 | ALK / ROS1 | ⭐⭐ | Small populations |
|---|
| 6 | HER2 | ⭐⭐⭐ | Big but already well exploited |
|---|
| 7 | TP53 | ⭐⭐⭐⭐ | Massive biology, but very hard and safety-limited |
|---|
Key distinction:
KRAS is commercially proven.
MYC is commercially transformational if solved.
Why MYC beats KRAS in long-term upside (even though KRAS “works” today)
KRAS inhibitors succeeded because:
Clear mutation
Enzyme-like pocket
Oncogene addiction
But:
KRAS drugs are mutation-restricted (e.g., G12C)
Resistance emerges quickly
Competitive crowding is intense
MYC, by contrast:
Is relevant across many mutations and lineages
Acts downstream of multiple resistance mechanisms
Could become a universal oncology control node
If MYC inhibition becomes feasible, it could outscale KRAS commercially, even if it takes longer.
The single biggest commercial risk with MYC
Therapeutic index.
MYC is important in normal cells:
Gut epithelium
Bone marrow
Hair follicles
Immune cells
So the commercial “win condition” is not maximal MYC suppression, but:
If a drug achieves functional MYC suppression in tumors without chronic systemic toxicity, the upside is enormous.
What pharma BD teams think (unspoken but real)
Internally, large pharma generally views MYC as:
That means:
Bottom line (commercial verdict)
If you could wave a wand and safely inhibit one oncogene:
It has:
The largest addressable biology,
The greatest combination leverage,
The most expansion potential beyond cancer,
And the highest ceiling for long-term value creation.
Everything else—KRAS included—is incremental by comparison.
